{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:39:41Z","timestamp":1793227181089,"version":"4.5.0"},"reference-count":352,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007801","name":"Fundaci\u00f3n S\u00e9neca","doi-asserted-by":"publisher","award":["20401\/SF\/17"],"award-info":[{"award-number":["20401\/SF\/17"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007801","name":"Fundaci\u00f3n S\u00e9neca","doi-asserted-by":"publisher","award":["19899\/GERM\/15"],"award-info":[{"award-number":["19899\/GERM\/15"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RYC2018-025622-I"],"award-info":[{"award-number":["RYC2018-025622-I"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-093528-B-I00"],"award-info":[{"award-number":["RTI2018-093528-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018779","name":"Fundaci\u00f3n Fero","doi-asserted-by":"publisher","award":["BFERO2020.01"],"award-info":[{"award-number":["BFERO2020.01"]}],"id":[{"id":"10.13039\/501100018779","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007406","name":"Fundaci\u00f3n BBVA","doi-asserted-by":"publisher","award":["LeonardoFellowship"],"award-info":[{"award-number":["LeonardoFellowship"]}],"id":[{"id":"10.13039\/100007406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["CB16\/10\/00239"],"award-info":[{"award-number":["CB16\/10\/00239"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Melatonin is one of the most phylogenetically conserved signals in biology. Although its original function was probably related to its antioxidant capacity, this indoleamine has been \u201cadopted\u201d by multicellular organisms as the \u201cdarkness signal\u201d when secreted in a circadian manner and is acutely suppressed by light at night by the pineal gland. However, melatonin is also produced by other tissues, which constitute its extrapineal sources. Apart from its undisputed chronobiotic function, melatonin exerts antioxidant, immunomodulatory, pro-apoptotic, antiproliferative, and anti-angiogenic effects, with all these properties making it a powerful antitumor agent. Indeed, this activity has been demonstrated to be mediated by interfering with various cancer hallmarks, and different epidemiological studies have also linked light at night (melatonin suppression) with a higher incidence of different types of cancer. In 2007, the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption, where melatonin plays a central role. Our aim is to review, from a global perspective, the role of melatonin both from pineal and extrapineal origin, as well as their possible interplay, as an intrinsic factor in the incidence, development, and progression of cancer. Particular emphasis will be placed not only on those mechanisms related to melatonin\u2019s antioxidant nature but also on the recently described novel roles of melatonin in microbiota and epigenetic regulation.<\/jats:p>","DOI":"10.3390\/antiox10020210","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T11:40:48Z","timestamp":1612179648000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Melatonin and Cancer: A Polyhedral Network Where the Source Matters"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9050-6448","authenticated-orcid":false,"given":"Maria-Angeles","family":"Bonmati-Carrion","sequence":"first","affiliation":[{"name":"Chronobiology Laboratory, Department of Physiology, IMIB-Arrixaca, University of Murcia, 30100 Murcia, Spain"},{"name":"Ciber Fragilidad y Envejecimiento Saludable, 28090 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Tomas-Loba","sequence":"additional","affiliation":[{"name":"Circadian Rhythm and Cancer Laboratory, Department of Physiology, IMIB-Arrixaca, University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1021\/ja01543a060","article-title":"Isolation of melatonin, the pineal gland factor that lightens melanocytes","volume":"80","author":"Lerner","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1530\/ror.0.0030013","article-title":"Melatonin and the pineal gland: Influence on mammalian seasonal and circadian physiology","volume":"3","author":"Arendt","year":"1998","journal-title":"Rev. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2011.00916.x","article-title":"Melatonin as a natural ally against oxidative stress: A physicochemical examination","volume":"51","author":"Galano","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1469-185X.2009.00118.x","article-title":"The changing biological roles of melatonin during evolution: From an antioxidant to signals of darkness, sexual selection and fitness","volume":"85","author":"Tan","year":"2010","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal melatonin: Sources, regulation, and potential functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2012.04.040","article-title":"Gene regulation by melatonin linked to epigenetic phenomena","volume":"503","author":"Korkmaz","year":"2012","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12574","article-title":"Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice","volume":"67","author":"Gao","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ren, W., Wang, P., Yan, J., Liu, G., Zeng, B., Hussain, T., Peng, C., Yin, J., Tan, B., and Li, T. (2018). Melatonin alleviates weanling stress in mice: Involvement of intestinal microbiota. J. Pineal Res., 64.","DOI":"10.1111\/jpi.12448"},{"key":"ref_9","first-page":"339","article-title":"Environmental risk factors for inflammatory bowel disease","volume":"6","author":"Molodecky","year":"2010","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/1120009X.2018.1541046","article-title":"Microbiota and cancer: An update","volume":"31","author":"Vallianou","year":"2019","journal-title":"J. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/BF01134354","article-title":"Pineal hormone melatonin oscillates also in the dinoflagellate Gonyaulax polyedra","volume":"78","author":"Balzer","year":"1991","journal-title":"Naturwissenschaften"},{"key":"ref_12","first-page":"391","article-title":"Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: Implications for an ancient antioxidant system","volume":"41","author":"Manchester","year":"1995","journal-title":"Cell. Mol. Biol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Balzer, I., H\u00f6cker, B., Kapp, H., and Bartolomaeus, B. (2000). Occurrence and comparative physiology of melatonin in evolutionary diverse organisms. The Redox State and Circadian Rhythms, Springer.","DOI":"10.1007\/978-94-015-9556-8_6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1600-079X.1999.tb00601.x","article-title":"Presence and effects of melatonin in Trypanosoma cruzi","volume":"27","author":"Reiter","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_15","first-page":"25","article-title":"Ubiquitous melatonin. Presence and effects in unicells, plants and animals","volume":"2","author":"Hardeland","year":"1996","journal-title":"Trends Comp. Biochem. Physiol. Sci. Open"},{"key":"ref_16","first-page":"211","article-title":"Melatonin in edible plants (phytomelatonin): Identification, concentrations, bioavailability and proposed functions","volume":"97","author":"Reiter","year":"2007","journal-title":"World Rev. Nutr. Diet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/jxb\/ern284","article-title":"Phytomelatonin: A review","volume":"60","author":"Paredes","year":"2009","journal-title":"J. Exp. Bot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1508\/cytologia.64.209","article-title":"Melatonin and other 5-methoxylated indoles in yeast: Presence in high concentrations and dependence on tryptophan availability","volume":"64","author":"Sprenger","year":"1999","journal-title":"Cytologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1051\/rnd:19990311","article-title":"Melatonin and 5-methoxytryptamine in non-metazoans","volume":"39","author":"Hardeland","year":"1999","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17207","DOI":"10.1073\/pnas.1900325116","article-title":"A productivity collapse to end Earth\u2019s Great Oxidation","volume":"116","author":"Hodgskiss","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jpi.12267","article-title":"Melatonin: An ancient molecule that makes oxygen metabolically tolerable","volume":"59","author":"Manchester","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1600-079X.2007.00536.x","article-title":"Photo-degradation of melatonin: Influence of argon, hydrogen peroxide, and ethanol","volume":"44","author":"Peschke","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1600-079X.1995.tb00147.x","article-title":"On the primary functions of melatonin in evolution: Mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals","volume":"18","author":"Hardeland","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_24","unstructured":"Gutenbrunner, C., Hildebrandt, G., and Moog, R. (1993). A hypothesis on the evolutionary origins of photoperiodism based on circadian rhythmicity of melatonin in phylogenetically distant organisms. Chronobiology & Chronomedicine, Verlag Peter Lang."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.lfs.2004.03.003","article-title":"Melatonin and mitochondrial function","volume":"75","author":"Leon","year":"2004","journal-title":"Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1177\/074873049701200606","article-title":"Melatonin receptors: Molecular biology of a new family of G protein-coupled receptors","volume":"12","author":"Reppert","year":"1997","journal-title":"J. Biol. Rhythms"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1034\/j.1600-079X.2003.02111.x","article-title":"Melatonin: A hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin","volume":"34","author":"Tan","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C153","DOI":"10.1016\/0303-7207(91)90087-9","article-title":"Melatonin: The chemical expression of darkness","volume":"79","author":"Reiter","year":"1991","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/j.1600-0625.2008.00767.x","article-title":"Melatonin as a major skin protectant: From free radical scavenging to DNA damage repair","volume":"17","author":"Fischer","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1600-079X.2007.00466.x","article-title":"Cultured rat cortical astrocytes synthesize melatonin: Absence of a diurnal rhythm","volume":"43","author":"Liu","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jns.2010.04.013","article-title":"Arylalkylamine N-acetyltransferase (AANAT) is expressed in astrocytes and melatonin treatment maintains AANAT in the gerbil hippocampus induced by transient cerebral ischemia","volume":"294","author":"Park","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1007\/s00018-008-8001-x","article-title":"Melatonin, hormone of darkness and more: Occurrence, control mechanisms, actions and bioactive metabolites","volume":"65","author":"Hardeland","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ribelayga, C., P\u00e9vet, P., and Simonneaux, V. (2000). HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the siberian hamster. Am. J. Physiol. Regul. Integr. Comp. Physiol., 278.","DOI":"10.1152\/ajpregu.2000.278.5.R1339"},{"key":"ref_34","first-page":"259","article-title":"Cytochemical investigation of acetyl-serotonin-transferase activity in the pineal gland","volume":"25","author":"Balogh","year":"1979","journal-title":"Cell. Mol. Biol. Incl. Cyto Enzym."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02463562","article-title":"Localizing acethyl-serotonin transferase by electron microscopy","volume":"46","author":"Somogyi","year":"1975","journal-title":"Histochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tan, D.X., Manchester, L.C., Qin, L., and Reiter, R.J. (2016). Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122124"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000145376","article-title":"A light and electron microscopic study of the pineal body of the nutria (myocastor coypus)","volume":"109","author":"Salisbury","year":"1981","journal-title":"Cells Tissues Organs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1469-7793.2001.t01-1-00261.x","article-title":"An action spectrum for melatonin suppression: Evidence for a novel non-rod, non-cone photoreceptor system in humans","volume":"535","author":"Thapan","year":"2001","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1126\/science.7434030","article-title":"Light suppresses melatonin secretion in humans","volume":"210","author":"Lewy","year":"1980","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1055\/s-2007-1011846","article-title":"Suppression of nocturnal plasma melatonin and 6-sulphatoxymelatonin by bright and dim light in man","volume":"19","author":"Bojkowski","year":"1987","journal-title":"Horm. Metab. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1600-079X.1989.tb00412.x","article-title":"Human melatonin suppression by light is intensity dependent","volume":"6","author":"McIntyre","year":"1989","journal-title":"J. Pineal Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1469-7793.2000.00695.x","article-title":"Sensitivity of the human circadian pacemaker to nocturnal light: Melatonin phase resetting and suppression","volume":"526","author":"Zeitzer","year":"2000","journal-title":"J. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1523\/JNEUROSCI.21-16-06405.2001","article-title":"Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor","volume":"21","author":"Brainard","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2114\/jpa2.26.113","article-title":"Variations in the light-induced suppression of nocturnal melatonin with special reference to variations in the pupillary light reflex in humans","volume":"26","author":"Yasukouchi","year":"2007","journal-title":"J. Physiol. Anthropol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"472","DOI":"10.20945\/2359-3997000000066","article-title":"A brief review about melatonin, a pineal hormone","volume":"62","year":"2018","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1210\/endo-91-5-1213","article-title":"Binding of melatonin to human and rat plasma proteins","volume":"91","author":"Cardinali","year":"1972","journal-title":"Endocrinology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0014-4835(78)90166-5","article-title":"Melatonin in the retina and the harderian gland. Ontogeny, diurnal variations and melatonin treatment","volume":"27","author":"Bubenik","year":"1978","journal-title":"Exp. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00441-003-0822-1","article-title":"Localization of Aa-nat mRNA in the rat retina by fluorescence in situ hybridization and laser capture microdissection","volume":"315","author":"Liu","year":"2004","journal-title":"Cell Tissue Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1096\/fj.07-8371com","article-title":"Localization of a circadian clock in mammalian photoreceptors","volume":"21","author":"Tosini","year":"2007","journal-title":"FASEB J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1210\/EN.2015-1267","article-title":"Unique regulation of the melatonin synthetic pathway in the retina of diurnal female Arvicanthis ansorgei (Rodentia)","volume":"156","author":"Gianesini","year":"2015","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9703","DOI":"10.1073\/pnas.0601940103","article-title":"Circadian organization of the mammalian retina","volume":"103","author":"Ruan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1017\/S0952523807070538","article-title":"Expression of circadian clock genes in retinal dopaminergic cells","volume":"24","author":"Dorenbos","year":"2007","journal-title":"Vis. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0304-3940(92)90138-W","article-title":"Melatonin synthesis in chicken retina: Effect of kainic acid-induced lesions on the diurnal rhythm and D2-dopamine receptor-mediated regulation of serotonin N-acetyltransferase activity","volume":"135","author":"Zawilska","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0006-8993(93)91725-8","article-title":"Melatonin synthesis and circadian tryptophan hydroxylase activity in chicken retina following destruction of serotonin immunoreactive amacrine and bipolar cells by kainic acid","volume":"601","author":"Thomas","year":"1993","journal-title":"Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.mce.2009.04.010","article-title":"The melatonin-producing system is fully functional in retinal pigment epithelium (ARPE-19)","volume":"307","author":"Zmijewski","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1210\/jc.2002-020683","article-title":"Melatonin synthesis enzymes in Macaca mulatta: Focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87)","volume":"87","author":"Coon","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yu, H.S., Pang, S.F., and Tang, P.L. (1981). Increase in the level of retinal melatonin and persistence of its diurnal rhythm in rats after pinealectomy. J. Endocrinol., 91.","DOI":"10.1677\/joe.0.0910477"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/0024-3205(83)90192-3","article-title":"Rhythms in immunoreactive melatonin in the retina and harderian gland of rats: Persistence after pinealectomy","volume":"32","author":"Reiter","year":"1983","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1167\/iovs.18-24957","article-title":"Ocular clocks: Adapting mechanisms for eye functions and health","volume":"59","author":"Buhr","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1600-079X.1999.tb00606.x","article-title":"Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates","volume":"27","author":"Siu","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1600-079X.1999.tb00582.x","article-title":"Melatonin as an antioxidant in retinal photoreceptors","volume":"26","author":"Marchiafava","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000265239","article-title":"Phagocytic activity of cultured retinal pigment epithelial cells from chick embryo: Inhibition by melatonin and cyclic AMP, and its reversal by taurine and cyclic GMP","volume":"15","author":"Ogino","year":"1983","journal-title":"Ophthal. Res."},{"key":"ref_63","first-page":"1640","article-title":"Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage","volume":"18","author":"Rosen","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.exger.2009.02.002","article-title":"Age-related changes in melatonin synthesis in rat extrapineal tissues","volume":"44","author":"Naranjo","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1385\/ENDO:27:2:189","article-title":"A review of the multiple actions of melatonin on the immune system","volume":"27","author":"Guerrero","year":"2005","journal-title":"Endocrine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1096\/fj.03-0694fje","article-title":"Evidence of melatonin synthesis by human lymphocytes and its physiological significance: Possible role as intracrine, autocrine, and\/or paracrine substance","volume":"18","author":"Calvo","year":"2004","journal-title":"FASEB J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1210\/jc.2004-1429","article-title":"Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2\/interleukin-2 receptor system","volume":"90","author":"Lardone","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1034\/j.1600-079X.2000.280401.x","article-title":"Evidence for melatonin synthesis in mouse and human bone marrow cells","volume":"28","author":"Conti","year":"2000","journal-title":"J. Pineal Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0304-4165(99)00125-7","article-title":"Identification of highly elevated levels of melatonin in bone marrow: Its origin and significance","volume":"1472","author":"Tan","year":"1999","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"C\u00f3rdoba-Moreno, M.O., de Souza, E.D.S., Quiles, C.L., dos Santos-Silva, D., Kinker, G.S., Muxel, S.M., Markus, R.P., and Fernandes, P.A. (2020). Rhythmic expression of the melatonergic biosynthetic pathway and its differential modulation in vitro by LPS and IL10 in bone marrow and spleen. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61652-5"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e12394","DOI":"10.1111\/jpi.12394","article-title":"Melatonin signaling in T cells: Functions and applications","volume":"62","author":"Ren","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.3390\/ijms14048638","article-title":"Melatonin: Buffering the immune system","volume":"14","author":"Lardone","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_73","first-page":"215","article-title":"Melatonin supplementation restores cellular proliferation and DNA synthesis in the splenic and thymic lymphocytes of old rats","volume":"24","author":"Reiter","year":"2003","journal-title":"Neuro Endocrinol Lett"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0047-6374(98)00046-3","article-title":"Melatonin: Immune modulation of spleen cells in young, middle-aged and senescent mice","volume":"103","author":"Atre","year":"1998","journal-title":"Mech. Ageing Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1111\/bph.14083","article-title":"Immune-pineal axis\u2014Acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes","volume":"175","author":"Markus","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/jpi.12279","article-title":"Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism","volume":"59","author":"Zampieri","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1600-079X.2005.00220.x","article-title":"Melatonin synthesis and melatonin-membrane receptor (MT1) expression during rat thymus development: Role of the pineal gland","volume":"39","author":"Guerrero","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.phrs.2009.11.014","article-title":"Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation","volume":"62","author":"Maldonado","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1600-079X.1992.tb00020.x","article-title":"The effect of food deprivation on brain and gastrointestinal tissue levels of tryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin","volume":"12","author":"Bubenik","year":"1992","journal-title":"J. Pineal Res."},{"key":"ref_80","first-page":"507","article-title":"Effect of food restriction on 24-h serum and pineal melatonin content in male rats","volume":"115","author":"Chik","year":"1987","journal-title":"Acta Endocrinol."},{"key":"ref_81","first-page":"627","article-title":"Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates","volume":"35","author":"Hattori","year":"1995","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.nut.2005.02.005","article-title":"Melatonin in walnuts: Influence on levels of melatonin and total antioxidant capacity of blood","volume":"21","author":"Reiter","year":"2005","journal-title":"Nutrition"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1600-079X.1996.tb00294.x","article-title":"Melatonin concentrations in serum and tissues of porcine gastrointestinal tract and their relationship to the intake and passage of food","volume":"21","author":"Bubenik","year":"1996","journal-title":"J. Pineal Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1749-6632.1994.tb56826.x","article-title":"Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin","volume":"719","author":"Huether","year":"1994","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1034\/j.1600-079x.2000.280102.x","article-title":"Circadian variation of portal, arterial and venous blood levels of melatonin in pigs and its relationship to food intake and sleep","volume":"28","author":"Bubenik","year":"2000","journal-title":"J. Pineal Res."},{"key":"ref_86","first-page":"101","article-title":"Melatonin in traditional Mediterranean diets","volume":"49","author":"Iriti","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"17252","DOI":"10.3402\/fnr.v56i0.17252","article-title":"Dietary factors and fluctuating levels of melatonin","volume":"56","author":"Peuhkuri","year":"2012","journal-title":"Food Nutr. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1600-079X.2011.00884.x","article-title":"Melatonin levels, determined by LC-ESI-MS\/MS, fluctuate during the day\/night cycle in Vitis vinifera cv Malbec: Evidence of its antioxidant role in fruits","volume":"51","author":"Boccalandro","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1600-079X.2011.00964.x","article-title":"Melatonin and serotonin profiles in beans of Coffea species","volume":"52","author":"Ramakrishna","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physiolgenomics.00095.2018","article-title":"Aging, melatonin biosynthesis, and circadian clockworks in the gastrointestinal system of the laboratory mouse","volume":"51","author":"Paulose","year":"2019","journal-title":"Physiol. Genomics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1073\/pnas.91.5.1824","article-title":"Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance","volume":"91","author":"Dollins","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0306-4565(01)00024-9","article-title":"The administration of exogenous melatonin during the daytime lowers the thermoregulatory setpoint in humans","volume":"27","author":"Aizawa","year":"2002","journal-title":"J. Therm. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Tsukamoto, K., Ariga, H., Mantyh, C., Pappas, T.N., Yanagi, H., Yamamura, T., and Takahashi, T. (2007). Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 293.","DOI":"10.1152\/ajpregu.00856.2006"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.2174\/092986710793348536","article-title":"Melatonin, a ootential therapeutic agent for smooth muscle-related pathological conditions and aging","volume":"17","author":"Pozo","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-079X.1986.tb00725.x","article-title":"The effect of serotonin, N-acetylserotonin, and melatonin on spontaneous contractions of isolated rat intestine","volume":"3","author":"Bubenik","year":"1986","journal-title":"J. Pineal Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-079X.1986.tb00750.x","article-title":"Effect of melatonin on the force of spontaneous contractions of in vitro rat small and large intestine","volume":"3","author":"Harlow","year":"1986","journal-title":"J. Pineal Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1023\/A:1020107915919","article-title":"Gastrointestinal melatonin: Localization, function, and clinical relevance","volume":"47","author":"Bubenik","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_98","first-page":"33","article-title":"Thirty four years since the discovery of gastrointestinal melatonin","volume":"59","author":"Bubenik","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1038\/sj.bjp.0701287","article-title":"Investigation into the contractile response of melatonin in the guinea-pig isolated proximal colon: The role of 5-HT4 and melatonin receptors","volume":"121","author":"Lucchelli","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1034\/j.1600-079X.2003.00044.x","article-title":"Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion","volume":"34","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"G1091","DOI":"10.1152\/ajpgi.00193.2003","article-title":"Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin","volume":"285","author":"Jedstedt","year":"2003","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1600-079X.2003.00103.x","article-title":"Central nervous \u03b11-adrenoceptor stimulation induces duodenal luminal release of melatonin","volume":"36","year":"2004","journal-title":"J. Pineal Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Flemstr\u00f6m, G., and Sj\u00f6blom, M. (2005). Epithelial cells and their neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol., 289.","DOI":"10.1152\/ajpgi.00093.2005"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1600-079X.1998.tb00395.x","article-title":"Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions","volume":"25","author":"Messner","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1016\/S0024-3205(99)00519-6","article-title":"High physiological levels of melatonin in the bile of mammals","volume":"65","author":"Tan","year":"1999","journal-title":"Life Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0024-3205(01)01143-2","article-title":"Presence of melatonin in the human hepatobiliary-gastrointestinal tract","volume":"69","author":"Messner","year":"2001","journal-title":"Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/0024-3205(92)90402-B","article-title":"Effect of tryptophan administration on circulating melatonin levels in chicks and rats: Evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract","volume":"51","author":"Huether","year":"1992","journal-title":"Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/molehr\/5.8.720","article-title":"Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation","volume":"5","year":"1999","journal-title":"Mol. Hum. Reprod."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/0277-5379(89)90122-3","article-title":"Endocrine and immune effects of melatonin therapy in metastatic cancer patients","volume":"25","author":"Lissoni","year":"1989","journal-title":"Eur. J. Cancer Clin. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1023\/A:1026656720868","article-title":"Melatonin reduces lipid peroxidation and tissue edema in cerulein- induced acute pancreatitis in rats","volume":"44","author":"Qi","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","article-title":"Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations","volume":"52","author":"Venegas","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S0140-6736(78)92591-6","article-title":"Role of pineal gland in etiology and treatment of breast cancer","volume":"312","author":"Cohen","year":"1978","journal-title":"Lancet"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1600-079X.2009.00665.x","article-title":"Defining chronodisruption","volume":"46","author":"Erren","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1080\/07420520701534624","article-title":"Euchronism, allochronism, and dyschronism: Is internal desynchronization of human circadian rhythms a sign of illness?","volume":"24","author":"Reinberg","year":"2007","journal-title":"Chronobiol. Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/07420520802256101","article-title":"Internal desynchronization of circadian rhythms and tolerance to shift work","volume":"25","author":"Reinberg","year":"2008","journal-title":"Chronobiol. Int."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.lfs.2017.02.008","article-title":"Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption","volume":"173","author":"Touitou","year":"2017","journal-title":"Life Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10552-005-9010-9","article-title":"Circadian disruption, shift work and the risk of cancer: A summary of the evidence and studies in Seattle","volume":"17","author":"Davis","year":"2006","journal-title":"Cancer Causes Control"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.mehy.2004.03.020","article-title":"Lighting for the human circadian clock: Recent research indicates that lighting has become a public health issue","volume":"63","author":"Pauley","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2017). Moving to the rhythm with clock (circadian) genes, autophagy, mTOR, and SIRT1 in degenerative disease and cancer. Curr. Neurovasc. Res., 14.","DOI":"10.2174\/1567202614666170718092010"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1158\/1055-9965.EPI-14-1271","article-title":"Increased and mistimed sex hormone production in night shift workers","volume":"24","author":"Papantoniou","year":"2015","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_121","first-page":"3038","article-title":"Marked 24-h rest\/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status","volume":"6","author":"Mormont","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_122","unstructured":"Sephton, S.E., Lush, E., Dedert, E.A., Floyd, A.R., Rebholz, W.N., Dhabhar, F.S., Spiegel, D., and Salmon, P. (2000). Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain. Behav. Immun., 92."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S1470-2045(07)70373-X","article-title":"Carcinogenicity of shift-work, painting, and fire-fighting","volume":"8","author":"Straif","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/oem.2009.053512","article-title":"Considerations of circadian impact for defining \u201cshift work\u201d in cancer studies: IARC Working Group Report","volume":"68","author":"Stevens","year":"2011","journal-title":"Occup. Environ. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/CEJ.0000000000000030","article-title":"Light exposure at night, sleep duration, melatonin, and breast cancer: A dose-response analysis of observational studies","volume":"23","author":"Yang","year":"2014","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1158\/1055-9965.EPI-08-0637","article-title":"Urinary melatonin levels and postmenopausal breast cancer risk in the nurses\u2019 health study cohort","volume":"18","author":"Schernhammer","year":"2009","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2014.07.008","article-title":"Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men","volume":"67","author":"Sigurdardottir","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"831","DOI":"10.7150\/jca.14573","article-title":"The reduction in circulating melatonin level may contribute to the pathogenesis of ovarian cancer: A retrospective study","volume":"7","author":"Zhao","year":"2016","journal-title":"J. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep29606","article-title":"Urinary melatonin-sulfate\/cortisol ratio and the presence of prostate cancer: A case-control study","volume":"6","author":"Tai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Majidinia, M., Sadeghpour, A., Mehrzadi, S., Reiter, R.J., Khatami, N., and Yousefi, B. (2017). Melatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways. J. Pineal Res., 63.","DOI":"10.1111\/jpi.12416"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: Under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/ars.2017.7290","article-title":"The role of sirtuins in antioxidant and redox signaling","volume":"28","author":"Singh","year":"2018","journal-title":"Antioxidants Redox Signal."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Mayo, J.C., Sainz, R.M., Gonz\u00e1lez Men\u00e9ndez, P., Cepas, V., Tan, D.X., and Reiter, R.J. (2017). Melatonin and sirtuins: A \u201cnot-so unexpected\u201d relationship. J. Pineal Res., 62.","DOI":"10.1111\/jpi.12391"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3109\/07420528.2012.667859","article-title":"The endogenous melatonin (MT) signal facilitates reentrainment of the circadian system to light-induced phase advances by acting upon MT2 receptors","volume":"29","author":"Pfeffer","year":"2012","journal-title":"Chronobiol. Int."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1600-079X.2006.00387.x","article-title":"Clock gene expression in the retina of melatonin-proficient (C3H) and melatonin-deficient (C57BL) mice","volume":"42","author":"Dinet","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Hiragaki, S., Baba, K., Coulson, E., Kunst, S., Spessert, R., and Tosini, G. (2014). Melatonin signaling modulates clock genes expression in the mouse retina. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106819"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12189","article-title":"Melatonin feedback on clock genes: A theory involving the proteasome","volume":"58","author":"Vriend","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10522-014-9495-2","article-title":"Differential role of melatonin in restoration of age-induced alterations in daily rhythms of expression of various clock genes in suprachiasmatic nucleus of male Wistar rats","volume":"15","author":"Mattam","year":"2014","journal-title":"Biogerontology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1600-079X.2010.00823.x","article-title":"Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model","volume":"50","author":"Schmit","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.0959-9673.2006.00474.x","article-title":"The role of melatonin in immuno-enhancement: Potential application in cancer","volume":"87","author":"Miller","year":"2006","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.pharep.2017.07.017","article-title":"Melatonin suppresses eosinophils and Th17 cells in hamsters treated with a combination of human liver fluke infection and a chemical carcinogen","volume":"70","author":"Wongsena","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_142","first-page":"581","article-title":"Melatonin enhances IL-2, IL-6, and IFN-y production by human circulating CD4+ cells","volume":"2","author":"Calvo","year":"1997","journal-title":"J. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1600-079X.2007.00548.x","article-title":"The antiproliferative activity of melatonin in B65 rat dopaminergic neuroblastoma cells is related to the downregulation of cell cycle-related genes","volume":"45","author":"Pizarro","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1600-079X.2004.00206.x","article-title":"Antiproliferative activity of melatonin by transcriptional inhibition of cyclin D1 expression: A molecular basis for melatonin-induced oncostatic effects","volume":"39","author":"Cini","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Lu, K.H., Lin, R.C., Yang, J.S., Yang, W.E., Reiter, R.J., and Yang, S.F. (2019). Molecular and cellular mechanisms of melatonin in osteosarcoma. Cells, 8.","DOI":"10.3390\/cells8121618"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.bone.2013.02.021","article-title":"Melatonin inhibits the proliferation of human osteosarcoma cell line MG-63","volume":"55","author":"Liu","year":"2013","journal-title":"Bone"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1600-079X.2012.00973.x","article-title":"Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells","volume":"53","author":"Wang","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1600-079X.2010.00824.x","article-title":"Melatonin and vitamin D 3 synergistically down-regulate Akt and MDM2 leading to TGF\u03b2-1-dependent growth inhibition of breast cancer cells","volume":"50","author":"Proietti","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cell.2008.09.034","article-title":"Telomerase reverse transcriptase delays aging in cancer-resistant mice","volume":"135","author":"Flores","year":"2008","journal-title":"Cell"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Grant, S.G., Melan, M.A., Latimer, J.J., and Witt-Enderby, P.A. (2009). Melatonin and breast cancer: Cellular mechanisms, clinical studies and future perspectives. Exp. Rev. Mol. Med., 11.","DOI":"10.1017\/S1462399409000982"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1600-079X.2010.00789.x","article-title":"Melatonin induces pro-apoptotic signaling pathway in human pancreatic carcinoma cells (PANC-1)","volume":"49","author":"Jaworek","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1600-079X.2006.00392.x","article-title":"Inhibition of proliferation and induction of apoptosis by melatonin in human myeloid HL-60 cells","volume":"42","author":"Rubio","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_153","first-page":"723","article-title":"Anti-gastric cancer effect of melatonin and Bcl-2, Bax, p21 and p53 expression changes","volume":"66","author":"Xu","year":"2014","journal-title":"Sheng Li Xue Bao"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnmol.2018.00093","article-title":"Melatonin regulates apoptosis and autophagy Via ROS-MST1 pathway in subarachnoid hemorrhage","volume":"11","author":"Shi","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.3892\/ol.2017.5785","article-title":"Melatonin treatment induces apoptosis through regulating the nuclear factor-\u03bab and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells","volume":"13","author":"Li","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.3892\/or.2016.5100","article-title":"Melatonin induces cell apoptosis in Mia PaCa-2 cells via the suppression of nuclear factor-\u03baB and activation of ERK and JNK: A novel therapeutic implication for pancreatic cancer","volume":"36","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-079X.2011.00865.x","article-title":"Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1\u03b1 inactivation in hypoxic PC-3 prostate cancer cells","volume":"51","author":"Cho","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/ceo.12802","article-title":"Hypoxia-induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia-inducible factors-1\u03b1 protein","volume":"45","author":"Lai","year":"2017","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_159","first-page":"4383","article-title":"Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells","volume":"58","author":"Cos","year":"1998","journal-title":"Cancer Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.bbamem.2008.11.005","article-title":"Loss of tight junction barrier function and its role in cancer metastasis","volume":"1788","author":"Martin","year":"2009","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_161","first-page":"3","article-title":"Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK\/MAPK pathway","volume":"9","author":"Zhou","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-015-0454-8","article-title":"Involvement of ROS-alpha v beta 3 integrin-FAK\/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia","volume":"13","author":"Xu","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Su, S.C., Hsieh, M.J., Yang, W.E., Chung, W.H., Reiter, R.J., and Yang, S.F. (2017). Cancer metastasis: Mechanisms of inhibition by melatonin. J. Pineal Res., 62.","DOI":"10.1111\/jpi.12370"},{"key":"ref_164","first-page":"1","article-title":"Effect of melatonin in epithelial mesenchymal transition markers and invasive properties of breast cancer stem cells of canine and human cell lines","volume":"11","author":"Colombo","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/jpi.12295","article-title":"Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C\/EBP\u03b2 and NF\u03baB cleavage","volume":"60","author":"Wu","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Basu, A.K. (2018). DNA damage, mutagenesis and cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040970"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000014569","article-title":"The oxidant\/antioxidant network: Role of melatonin","volume":"8","author":"Reiter","year":"1999","journal-title":"Neurosignals"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0891-5849(98)00226-3","article-title":"Antioxidant properties of melatonin: A pulse radiolysis study","volume":"26","author":"Mahal","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1749-6632.2000.tb05402.x","article-title":"Melatonin and its relation to the immune system and inflammation","volume":"917","author":"Reiter","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jpi.12514","article-title":"Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection","volume":"65","author":"Galano","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s002040100219","article-title":"In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats","volume":"75","author":"Gultekin","year":"2001","journal-title":"Arch. Toxicol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1034\/j.1600-079x.2001.310207.x","article-title":"Melatonin versus vitamin E as protective treatment against oxidative stress after extra-hepatic bile duct ligation in rats","volume":"31","author":"Montilla","year":"2001","journal-title":"J. Pineal Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1562\/0031-8655(2003)078<0449:IOSMOW>2.0.CO;2","article-title":"Interaction of singlet molecular oxygen with melatonin and related indoles","volume":"78","author":"Matuszak","year":"2003","journal-title":"Photochem. Photobiol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1600-079X.1995.tb00163.x","article-title":"Melatonin protects neurons from singlet oxygen-induced apoptosis","volume":"18","author":"Cagnoli","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1600-079X.1998.tb00361.x","article-title":"The interaction of melatonin and its precursors with aluminium, cadmium, copper, iron, lead, and zinc: An adsorptive voltammetric study","volume":"24","author":"Limson","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1034\/j.1600-079X.2003.00058.x","article-title":"Melatonin prevents free radical formation due to the interaction between \u03b2-amyloid peptides and metal ions [Al(III), Zn(II), Cu(II), Mn(II), Fe(II)]","volume":"35","author":"Zatta","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1034\/j.1600-079X.2002.01859.x","article-title":"Melatonin protects against copper-mediated free radical damage","volume":"32","author":"Parmar","year":"2002","journal-title":"J. Pineal Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0304-4165(02)00527-5","article-title":"Protection against oxidative protein damage induced by metal-catalyzed reaction or alkylperoxyl radicals: Comparative effects of melatonin and other antioxidants","volume":"1620","author":"Mayo","year":"2003","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/jpi.12132","article-title":"A review of metal-catalyzed molecular damage: Protection by melatonin","volume":"56","author":"Romero","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_180","first-page":"87","article-title":"Melatonin, a mediator of electron transfer and repair reactions, acts synergistically with the chain-breaking antioxidants ascorbate, trolox and glutathione","volume":"17","author":"Poeggeler","year":"1995","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1211\/0022357011777747","article-title":"Individual and synergistic antioxidative actions of melatonin: Studies with vitamin E, vitamin C, glutathione and desferrrioxamine (desferoxamine) in rat liver homogenates","volume":"53","author":"Gitto","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.mrgentox.2007.07.013","article-title":"Protective action of melatonin against oxidative DNA damage-Chemical inactivation versus base-excision repair","volume":"634","author":"Sliwinski","year":"2007","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Davanipour, Z., Poulsen, H.E., Weimann, A., and Sobel, E. (2009). Endogenous melatonin and oxidatively damaged guanine in DNA. BMC Endocr. Disord., 9.","DOI":"10.1186\/1472-6823-9-22"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Ferreira, S.G., Peliciari-Garcia, R.A., Takahashi-Hyodo, S.A., Rodrigues, A.C., Amaral, F.G., Berra, C.M., Bordin, S., Curi, R., and Cipolla-Neto, J. (2013). Effects of melatonin on DNA damage induced by cyclophosphamide in rats. Braz. J. Med. Biol. Res., 46.","DOI":"10.1590\/1414-431X20122230"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Liu, R., Fu, A., Hoffman, A.E., Zheng, T., and Zhu, Y. (2013). Melatonin enhances DNA repair capacity possibly by affecting genes involved in DNA damage responsive pathways. BMC Cell Biol., 14.","DOI":"10.1186\/1471-2121-14-1"},{"key":"ref_186","first-page":"27","article-title":"Expression levels of two dna repair-related genes under 8 gy ionizing radiation and 100 mg\/kg melatonin delivery in rat peripheral blood","volume":"7","author":"Valizadeh","year":"2017","journal-title":"J. Biomed. Phys. Eng."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1038\/onc.2011.469","article-title":"Melatonin triggers p53 Ser phosphorylation and prevents DNA damage accumulation","volume":"31","author":"Santoro","year":"2012","journal-title":"Oncogene"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1600-079X.2005.00248.x","article-title":"A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes","volume":"39","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.mrgentox.2013.01.005","article-title":"Melatonin ameliorates bisphenol A-induced DNA damage in the germ cells of adult male rats","volume":"752","author":"Wu","year":"2013","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1055\/s-0043-119881","article-title":"Effect of melatonin supplementation on antioxidant status and DNA damage in high intensity trained athletes","volume":"38","author":"Planells","year":"2017","journal-title":"Int. J. Sports Med."},{"key":"ref_191","first-page":"11","article-title":"Medical implications of melatonin: Receptor-mediated and receptor-independent actions","volume":"52","author":"Reiter","year":"2007","journal-title":"Adv. Med. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/BF02253360","article-title":"Actions of melatonin in the reduction of oxidative stress: A review","volume":"7","author":"Reiter","year":"2000","journal-title":"J. Biomed. Sci."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0197-0186(94)00154-M","article-title":"Melatonin stimulates brain glutathione peroxidase activity","volume":"26","author":"Reiter","year":"1995","journal-title":"Neurochem. Int."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1600-079X.1995.tb00178.x","article-title":"Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks","volume":"19","author":"Pablos","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1600-079X.2010.00792.x","article-title":"Protective effect of melatonin against Opisthorchis viverrini-induced oxidative and nitrosative DNA damage and liver injury in hamsters","volume":"49","author":"Laothong","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"429","DOI":"10.17219\/acem\/43888","article-title":"The effects of melatonin on oxidative stress parameters and DNA fragmentation in testicular tissue of rats exposed to microwave radiation","volume":"24","author":"Sokolovic","year":"2015","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Bondy, S.C., and Campbell, A. (2018). Mechanisms underlying tumor suppressive properties of melatonin. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082205"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1517\/14728222.2013.834890","article-title":"Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: A review","volume":"17","author":"Bizzarri","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.3390\/ijms14023901","article-title":"A comparison of B16 melanoma cells and 3T3 fibroblasts concerning cell viability and ROS production in the presence of melatonin, tested over a wide range of concentrations","volume":"14","author":"Hardeland","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.redox.2018.01.015","article-title":"Redox control of cancer cell destruction","volume":"16","author":"Regdon","year":"2018","journal-title":"Redox Biol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/bs.acr.2019.03.004","article-title":"Immunometabolism: A new target for improving cancer immunotherapy","volume":"143","author":"Guo","year":"2019","journal-title":"Adv. Cancer Res."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"Cairns","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrc1187","article-title":"Targeting HIF-1 for cancer therapy","volume":"3","author":"Semenza","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic reprogramming: A cancer hallmark even Warburg did not anticipate","volume":"21","author":"Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_205","first-page":"1","article-title":"Melatonin combined with endoplasmic reticulum stress induces cell death via the PI3K\/Akt\/mTOR pathway in B16F10 melanoma cells","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"R271","DOI":"10.1093\/hmg\/ddl207","article-title":"Molecular components of the mammalian circadian clock","volume":"15","author":"Ko","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Buhr, E.D., and Takahashi, J.S. (2013). Molecular components of the mammalian circadian clock. Handb. Exp. Pharmacol., 3\u201327.","DOI":"10.1007\/978-3-642-25950-0_1"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Goriki, A., Hatanaka, F., Myung, J., Kim, J.K., Yoritaka, T., Tanoue, S., Abe, T., Kiyonari, H., Fujimoto, K., and Kato, Y. (2014). A novel protein, CHRONO, functions as a core component of the mammalian circadian clock. PLoS Biol., 12.","DOI":"10.1371\/journal.pbio.1001839"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Pett, J.P., Koren\u010di\u010d, A., Wesener, F., Kramer, A., and Herzel, H. (2016). Feedback loops of the mammalian circadian clock constitute repressilator. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1005266"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1126\/science.1171641","article-title":"Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis","volume":"324","author":"Ramsey","year":"2009","journal-title":"Science"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/j.cell.2013.11.034","article-title":"Reprogramming of the circadian clock by nutritional challenge","volume":"155","author":"Patel","year":"2013","journal-title":"Cell"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"653017","DOI":"10.1155\/2014\/653017","article-title":"PPARs integrate the mammalian clock and energy metabolism","volume":"2014","author":"Chen","year":"2014","journal-title":"PPAR Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cell.2008.07.002","article-title":"The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control","volume":"134","author":"Nakahata","year":"2008","journal-title":"Cell"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biocel.2008.08.035","article-title":"Chromatin remodeling, metabolism and circadian clocks: The interplay of CLOCK and SIRT1","volume":"41","author":"Grimaldi","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1038\/emm.2013.65","article-title":"AMP-activated protein kinase as a key molecular link between metabolism and clockwork","volume":"45","author":"Lee","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1126\/science.1180067","article-title":"Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock","volume":"327","author":"Robles","year":"2010","journal-title":"Science"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.molcel.2014.01.028","article-title":"Phosphorylation of LSD1 by PKC\u03b1 is crucial for circadian rhythmicity and phase resetting","volume":"53","author":"Nam","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_218","first-page":"128","article-title":"Melatonin and circadian oscillators in aging\u2014A dynamic approach to the multiply connected players","volume":"40","author":"Hardeland","year":"2014","journal-title":"Interdisc. Top. Gerontol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/MOL.0b013e3283292399","article-title":"Chronobiology, genetics and metabolic syndrome","volume":"20","author":"Garaulet","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/ijo.2010.118","article-title":"The chronobiology, etiology and pathophysiology of obesity","volume":"34","author":"Garaulet","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.neuroscience.2006.09.030","article-title":"Melatonin affects nuclear orphan receptors mRNA in the rat suprachiasmatic nuclei","volume":"144","author":"Agez","year":"2007","journal-title":"Neuroscience"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.2845576","article-title":"Putative melatonin receptors in a human biological clock","volume":"242","author":"Reppert","year":"1988","journal-title":"Science"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1600-079X.1993.tb00522.x","article-title":"Pineal modulation of the rat caudate-putamen spontaneous neuronal activity: Roles of melatonin and vasotocin","volume":"15","author":"Reiter","year":"1993","journal-title":"J. Pineal Res."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1046\/j.1365-2826.2001.00656.x","article-title":"Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum","volume":"13","author":"Escames","year":"2001","journal-title":"J. Neuroendocrinol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/j.1365-2826.2004.01250.x","article-title":"Mechanisms of N-methyl-D-aspartate receptor inhibition by melatonin in the rat striatum","volume":"16","author":"Escames","year":"2004","journal-title":"J. Neuroendocrinol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.neurol.2014.05.008","article-title":"The internal time-giver role of melatonin. A key for our health","volume":"170","year":"2014","journal-title":"Rev. Neurol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1042\/CBI20100036","article-title":"Melatonin as the most effective organizer of the rhythm of protein synthesis in hepatocytes in vitro and in vivo","volume":"34","author":"Brodsky","year":"2010","journal-title":"Cell Biol. Int."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1600-079X.2008.00610.x","article-title":"Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes","volume":"45","author":"Andreotti","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_229","first-page":"80","article-title":"Circadian modulation of sodium-potassium ATPase and sodium-proton exchanger in human erythrocytes: In vitro effect of melatonin\u2014PubMed","volume":"57","author":"Chakravarty","year":"2011","journal-title":"Cell. Mol Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s00018-018-2963-0","article-title":"Mitochondrial functions and melatonin: A tour of the reproductive cancers","volume":"76","author":"Seiva","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1002\/cam4.2035","article-title":"Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers","volume":"8","author":"Liu","year":"2019","journal-title":"Cancer Med."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/carcin\/bgi075","article-title":"Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers","volume":"26","author":"Chen","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/sj.cgt.7701061","article-title":"Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL\/6 mice","volume":"14","author":"Hua","year":"2007","journal-title":"Cancer Gene Ther."},{"key":"ref_234","first-page":"1201","article-title":"Clock gene mouse period2 overexpression inhibits growth of human pancreatic cancer cells and has synergistic effect with cisplatin","volume":"29","author":"Akira","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11033-013-2841-7","article-title":"Deregulated expression of circadian clock and clock-controlled cell cycle genes in chronic lymphocytic leukemia","volume":"41","author":"Rana","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Liu, L., Wang, Z., Cao, J., Dong, Y., and Chen, Y. (2019). Effect of melatonin on monochromatic light-induced changes in clock gene circadian expression in the chick liver. J. Photochem. Photobiol. B Biol., 197.","DOI":"10.1016\/j.jphotobiol.2019.111537"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.lfs.2014.08.024","article-title":"Melatonin as a proteasome inhibitor. is there any clinical evidence?","volume":"115","author":"Vriend","year":"2014","journal-title":"Life Sci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.cell.2013.05.027","article-title":"XSIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1210\/en.2015-2027","article-title":"Clock and BMAL1 regulate muscle insulin sensitivity via SIRT1 in male mice","volume":"157","author":"Liu","year":"2016","journal-title":"Endocrinology"},{"key":"ref_240","first-page":"423","article-title":"The modulatory role of melatonin on immune responsiveness","volume":"7","author":"Reiter","year":"2006","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1089\/jir.1990.10.403","article-title":"Interferon-\u03b3 modulates melatonin production in rat pineal glands in organ culture","volume":"10","author":"Withyachumnarnkul","year":"1990","journal-title":"J. Interferon Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0165-5728(94)00146-F","article-title":"Effect of granulocyte-macrophage colony stimulating factor and granulocyte colony stimulating factor on melatonin secretion in rats in vivo and in vitro studies","volume":"56","author":"Komorowski","year":"1995","journal-title":"J. Neuroimmunol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"526464","DOI":"10.1155\/2015\/526464","article-title":"Interleukin-1\u03b2 modulates melatonin secretion in ovine pineal gland: Ex vivo study","volume":"2015","author":"Herman","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1600-079X.1996.tb00268.x","article-title":"A role for bursa fabricii and bursin in the ontogeny of the pineal biosynthetic activity in the chicken","volume":"21","author":"Boudard","year":"1996","journal-title":"J. Pineal Res."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1007\/s00018-010-0374-y","article-title":"Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells","volume":"67","author":"Lardone","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1600-079X.2006.00345.x","article-title":"Injury switches melatonin production source from endocrine (pineal) to paracrine (phagocytes)\u2014Melatonin in human colostrum and colostrum phagocytes","volume":"41","author":"Pontes","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0052010","article-title":"NF-\u03baB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) gene","volume":"7","author":"Muxel","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0165-5728(99)00271-4","article-title":"Exogenous melatonin: Quantitative enhancement in vivo of cells mediating non-specific immunity","volume":"104","author":"Currier","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jpi.12075","article-title":"The role of melatonin in the cells of the innate immunity: A review","volume":"55","author":"Calvo","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_250","doi-asserted-by":"crossref","unstructured":"Nied\u017awiecki, M., Budzi\u0142o, O., Adamkiewicz-Dro\u017cy\u0144ska, E., Pawlik-Gwozdecka, D., Zieli\u0144ski, M., Maciejka-Kemb\u0142owska, L., Szczepa\u0144ski, T., and Trzonkowski, P. (2019). CD4+CD25highCD127low\/-Foxp3+regulatory T-cell population in acute leukemias: A review of the literature. J. Immunol. Res., 2019.","DOI":"10.1155\/2019\/2816498"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.canlet.2004.05.003","article-title":"RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line","volume":"216","author":"Guerrero","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.lfs.2019.05.009","article-title":"Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review","volume":"228","author":"Mortezaee","year":"2019","journal-title":"Life Sci."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4196\/kjpp.2008.12.2.37","article-title":"Melatonin induces Akt phosphorylation through Melatonin receptor- and PI3K-Dependent pathways in primary astrocytes","volume":"12","author":"Kong","year":"2008","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"56698","DOI":"10.18632\/oncotarget.18082","article-title":"Inhibition of the PI3K\/AKT\/mTOR pathway activates autophagy and compensatory Ras\/Raf\/MEK\/ERK signalling in prostate cancer","volume":"8","author":"Butler","year":"2017","journal-title":"Oncotarget"},{"key":"ref_256","doi-asserted-by":"crossref","unstructured":"Talib, W.H. (2018). Melatonin and cancer hallmarks. Molecules, 23.","DOI":"10.3390\/molecules23030518"},{"key":"ref_257","unstructured":"Cancer, W.I.A.F.R. (2020, December 22). On GLOBOCAN 2020. Available online: https:\/\/www.uicc.org\/news\/globocan-2020-new-cancer-data."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/sj.bjc.6601626","article-title":"Melatonin and cancer risk: Does light at night compromise physiologic cancer protection by lowering serum melatonin levels?","volume":"90","author":"Schernhammer","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_259","first-page":"3271948","article-title":"Melatonin: An anti-tumor agent in hormone-dependent cancers","volume":"2018","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1093\/jnci\/93.20.1563","article-title":"Rotating night shifts and risk of breast cancer in women participating in the nurses\u2019 health study","volume":"93","author":"Schernhammer","year":"2001","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/BF01613283","article-title":"Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: Potential involvement of antiestrogenic mechanisms in vivo","volume":"117","author":"Blask","year":"1991","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1096\/fasebj.13.8.857","article-title":"Melatonin blocks the activation of estrogen receptor for DNA binding","volume":"13","author":"Rato","year":"1999","journal-title":"FASEB J."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"133","DOI":"10.32794\/mr11250026","article-title":"Clock genes and the role of melatonin in cancer cells: An overview","volume":"2","author":"Chuffa","year":"2019","journal-title":"Melatonin Res."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.4161\/15384101.2014.954454","article-title":"Loss of circadian clock gene expression is associated with tumor progression in breast cancer","volume":"13","author":"Cadenas","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_265","first-page":"1","article-title":"Induction of the CLOCK gene by E2-ER\u03b1 signaling promotes the proliferation of breast cancer cells","volume":"9","author":"Xiao","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1600-079X.2011.00940.x","article-title":"Melatonin interferes in the desmoplastic reaction in breast cancer by regulating cytokine production","volume":"52","author":"Cos","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/jpi.12007","article-title":"Regulation of vascular endothelial growth factor by melatonin in human breast cancer cells","volume":"54","author":"Cos","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1006\/taap.2000.9115","article-title":"Disruption of mitochondrial respiration by melatonin in MCF-7 cells","volume":"171","author":"Scott","year":"2001","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1007\/s00018-017-2612-z","article-title":"Melatonin, mitochondria, and the cancer cell","volume":"74","author":"Proietti","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1593\/neo.07595","article-title":"Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors","volume":"9","author":"Winter","year":"2007","journal-title":"Neoplasia"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1740-3391-6-4","article-title":"Period-2: A tumor suppressor gene in breast cancer","volume":"6","author":"Xiang","year":"2008","journal-title":"J. Circad. Rhythms"},{"key":"ref_272","first-page":"1","article-title":"An overview of the polymorphisms of circadian genes associated with endocrine cancer","volume":"10","author":"Morell","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1038\/onc.2014.203","article-title":"Dual inhibition of REV-ERB\u03b2 and autophagy as a novel pharmacological approach to induce cytotoxicity in cancer cells","volume":"34","author":"Ercolani","year":"2015","journal-title":"Oncogene"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1158\/1940-6207.CAPR-09-0127","article-title":"The core circadian gene cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling","volume":"3","author":"Hoffman","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_275","first-page":"60","article-title":"Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells","volume":"49","author":"Huang","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12916-018-1010-1","article-title":"Circadian pathway genetic variation and cancer risk: Evidence from genome-wide association studies","volume":"16","author":"Mocellin","year":"2018","journal-title":"BMC Med."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"9315","DOI":"10.1158\/0008-5472.CAN-09-0648","article-title":"Testing the circadian gene hypothesis in prostate cancer: A population-based case-control study","volume":"69","author":"Zhu","year":"2009","journal-title":"Cancer Res."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrgastro.2016.8","article-title":"Circadian rhythms of liver physiology and disease: Experimental and clinical evidence","volume":"13","author":"Tahara","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"e12506","DOI":"10.1111\/jpi.12506","article-title":"Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine-induced hepatocellular carcinoma","volume":"65","author":"Crespo","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3748\/wjg.v20.i8.1986","article-title":"Clock genes: Their role in colorectal cancer","volume":"20","author":"Karantanos","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/codi.12847","article-title":"Expression of core clock genes in colorectal tumour cells compared with normal mucosa: A systematic review of clinical trials","volume":"17","author":"Fonnes","year":"2015","journal-title":"Color. Dis."},{"key":"ref_282","first-page":"5319","article-title":"Expression of circadian clock genes in human colorectal adenoma and carcinoma","volume":"14","author":"Momma","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.3892\/ijo.2017.3987","article-title":"Upregulation of circadian gene \u201chClock\u201d contribution to metastasis of colorectal cancer","volume":"50","author":"Yaping","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1158\/1055-9965.EPI-16-1030","article-title":"Circadian disruption and prostate cancer risk: An updated review of epidemiological evidences","volume":"26","author":"Menegaux","year":"2017","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_285","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Rosales-Corral, S.A., Tan, D.X., Acuna-Castroviejo, D., Qin, L., Yang, S.F., and Xu, K. (2017). Melatonin, a full service anti-cancer agent: Inhibition of initiation, progression and metastasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040843"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1600-079X.1987.tb00870.x","article-title":"Effects of olfactory bulbectomy, melatonin, and\/or pinealectomy on three sublines of the dunning R3327 rat prostatic adenocarcinoma","volume":"4","author":"Toma","year":"1987","journal-title":"J. Pineal Res."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/1097-0045(20001101)45:3<238::AID-PROS6>3.0.CO;2-W","article-title":"Growth-inhibitory activity of melatonin on human androgen-independent DU 145 prostate cancer cells","volume":"45","author":"Limonta","year":"2000","journal-title":"Prostate"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1600-079X.2008.00585.x","article-title":"Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro","volume":"45","author":"Sainz","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1600-079X.2009.00682.x","article-title":"Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: Therapeutic implications for prostate cancer","volume":"47","author":"Joo","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/PL00000842","article-title":"Evaluation of signal transduction pathways mediating the nuclear exclusion of the androgen receptor by melatonin","volume":"58","author":"Lupowitz","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1600-079X.2012.01026.x","article-title":"Melatonin MT1 receptor-induced transcriptional up-regulation of p27Kip1 in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF-\u03baB): Potential implications on prostate cancer chemoprevention and","volume":"54","author":"Shiu","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_292","doi-asserted-by":"crossref","unstructured":"Hevia, D., Gonzalez-Menendez, P., Fernandez-Fernandez, M., Cueto, S., Rodriguez-Gonzalez, P., Garcia-Alonso, J.I., Mayo, J.C., and Sainz, R.M. (2017). Melatonin decreases glucose metabolism in prostate cancer cells: A 13C stable isotope-resolved metabolomic study. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081620"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"39896","DOI":"10.18632\/oncotarget.16379","article-title":"Bin Melatonin for the prevention and treatment of cancer","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cell.2015.03.015","article-title":"Time for food: The intimate interplay between nutrition, metabolism, and the circadian clock","volume":"161","author":"Asher","year":"2015","journal-title":"Cell"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2147\/NSS.S186665","article-title":"Sleep disturbances in patients with liver cirrhosis: Prevalence, impact, and management challenges","volume":"10","author":"Bruyneel","year":"2018","journal-title":"Nat. Sci. Sleep"},{"key":"ref_296","unstructured":"(2020, December 28). Key Facts in Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_298","doi-asserted-by":"crossref","unstructured":"Zhang, J.J., Meng, X., Li, Y., Zhou, Y., Xu, D.P., Li, S., and Li, H. (2017). Bin Effects of melatonin on liver injuries and diseases. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040673"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12944-015-0081-7","article-title":"Melatonin: A potential intervention for hepatic steatosis","volume":"14","author":"Sun","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1600-079X.2006.00346.x","article-title":"Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats","volume":"41","author":"Pan","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.trsl.2015.04.002","article-title":"Melatonin attenuates carbon tetrachloride-induced liver fibrosis via inhibition of necroptosis","volume":"166","author":"Choi","year":"2015","journal-title":"Transl. Res."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1139\/cjpp-2015-0266","article-title":"Therapeutic value of melatonin post-treatment on CCl4-induced fibrotic rat liver","volume":"94","author":"Mortezaee","year":"2016","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/j.lfs.2005.04.013","article-title":"Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress","volume":"77","author":"Wang","year":"2005","journal-title":"Life Sci."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"85655","DOI":"10.18632\/oncotarget.21107","article-title":"Association of melatonin membrane receptor 1A\/1B gene polymorphisms with the occurrence and metastasis of hepatocellular carcinoma","volume":"8","author":"Su","year":"2017","journal-title":"Oncotarget"},{"key":"ref_305","doi-asserted-by":"crossref","unstructured":"Wang, T.H., Hsueh, C., Chen, C.C., Li, W.S., Yeh, C.T., Lian, J.H., Chang, J.L., and Chen, C.Y. (2018). Melatonin inhibits the progression of hepatocellular carcinoma through microRNA let7i-3p mediated RAF1 reduction. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092687"},{"key":"ref_306","unstructured":"WHO (2020, December 03). International Agency for Research on Cancer GLOBOCAN. Available online: https:\/\/gco.iarc.fr\/today\/data\/factsheets\/populations\/900-world-fact-sheets.pdf."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/jcp.29049","article-title":"Melatonin: An important anticancer agent in colorectal cancer","volume":"235","author":"Mohammadzadeh","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_308","first-page":"89","article-title":"Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors","volume":"14","author":"Rawla","year":"2019","journal-title":"Prz. Gastroenterol."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1600-079X.1999.tb00612.x","article-title":"Melatonin content in plasma and large intestine of patients with colorectal carcinoma before and after surgery","volume":"27","author":"Vician","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"984","DOI":"10.4161\/cc.27868","article-title":"Functional genomics identify Birc5\/Survivin as a candidate gene involved in the chronotoxicity of cyclin-dependent kinase inhibitors","volume":"13","author":"Dulong","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1093\/carcin\/18.8.1549","article-title":"Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats","volume":"18","author":"Anisimov","year":"1997","journal-title":"Carcinogenesis"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3835(02)00090-3","article-title":"Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats","volume":"183","author":"Anisimov","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_313","first-page":"473","article-title":"Epitalon and colon carcinogenesis in rats: Proliferative activity and apoptosis in colon tumors and mucosa","volume":"12","author":"Kossoy","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_314","first-page":"1401","article-title":"Melatonin and colon carcinogenesis. IV. Effect of melatonin on proliferative activity and expression of apoptosis-related proteins in the spleen of rats exposed to 1,2-dimethylhydrazine","volume":"7","author":"Kossoy","year":"2000","journal-title":"Oncol. Rep."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1034\/j.1600-079x.2001.310213.x","article-title":"Melatonin and RZR\/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer","volume":"31","author":"Winczyk","year":"2001","journal-title":"J. Pineal Res."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1159\/000068569","article-title":"Possible involvement of the nuclear RZR\/ROR-alpha receptor in the antitumor action of melatonin on murine colon 38 cancer","volume":"23","author":"Winczyk","year":"2002","journal-title":"Tumor Biol."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/mc.22274","article-title":"Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis-associated colon carcinogenesis","volume":"55","author":"Trivedi","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jpi.12226","article-title":"Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation","volume":"58","author":"Wei","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/jpi.12131","article-title":"Melatonin reduces endothelin-1 expression and secretion in colon cancer cells through the inactivation of FoxO-1 and NF-\u03ba\u03b2","volume":"56","author":"Casado","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_320","first-page":"246","article-title":"Melatonin: Lowering the high price of free radicals","volume":"15","author":"Reiter","year":"2000","journal-title":"News Physiol. Sci."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/10409230903044914","article-title":"Reducing oxidative\/nitrosative stress: A newly-discovered genre for melatonin melatonin as an antioxidant","volume":"44","author":"Reiter","year":"2009","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tox.2010.04.008","article-title":"Melatonin: Action as antioxidant and potential applications in human disease and aging","volume":"278","author":"Collin","year":"2010","journal-title":"Toxicology"},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2015.00112","article-title":"Gut melatonin in vertebrates: Chronobiology and physiology","volume":"6","author":"Mukherjee","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12275-020-0094-4","article-title":"Melatonin attenuates microbiota dysbiosis of jejunum in short-term sleep deprived mice","volume":"58","author":"Gao","year":"2020","journal-title":"J. Microbiol."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5217\/ir.2019.00093","article-title":"Melatonin in the colon modulates intestinal microbiota in response to stress and sleep deprivation","volume":"18","author":"Park","year":"2020","journal-title":"Intest. Res."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1155\/2018\/2607679","article-title":"Effects of melatonin on intestinal microbiota and oxidative stress in colitis mice","volume":"2018","author":"Zhu","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_327","first-page":"1","article-title":"Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_328","doi-asserted-by":"crossref","unstructured":"Chuffa, G.G.A., Fioruci-Fontanelli, B.A., Mendes, L.O., Ferreira Seiva, F.R., Martinez, M., F\u00e1varo, W.J., Domeniconi, R.F., Pinheiro, P.F.F., Delazari dos Santos, L., and Martinez, F.E. (2015). Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1032-4"},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0146643","article-title":"Human gut bacteria are sensitive to melatonin and express endogenous circadian rhythmicity","volume":"11","author":"Paulose","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_330","doi-asserted-by":"crossref","unstructured":"Hong, F., Pan, S., Xu, P., Xue, T., Wang, J., Guo, Y., Jia, L., Qiao, X., Li, L., and Zhai, Y. (2020). Melatonin orchestrates lipid homeostasis through the hepatointestinal circadian clock and microbiota during constant light exposure. Cells, 9.","DOI":"10.3390\/cells9020489"},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/oby.2011.111","article-title":"Responses of gut microbiota to diet composition and weight loss in lean and obese mice","volume":"20","author":"Ravussin","year":"2012","journal-title":"Obesity"},{"key":"ref_332","doi-asserted-by":"crossref","unstructured":"Queipo-Ortu\u00f1o, M.I., Seoane, L.M., Murri, M., Pardo, M., Gomez-Zumaquero, J.M., Cardona, F., Casanueva, F., and Tinahones, F.J. (2013). Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065465"},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"367","DOI":"10.5056\/jnm18071","article-title":"Role of gut microbiota-gut hormone axis in the pathophysiology of functional gastrointestinal disorders","volume":"24","author":"Fukui","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1210\/me.2014-1108","article-title":"Minireview: Gut microbiota: The neglected endocrine organ","volume":"28","author":"Clarke","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_335","doi-asserted-by":"crossref","unstructured":"Vivarelli, S., Salemi, R., Candido, S., Falzone, L., Santagati, M., Stefani, S., Torino, F., Banna, G.L., Tonini, G., and Libra, M. (2019). Gut microbiota and cancer: From pathogenesis to therapy. Cancers, 11.","DOI":"10.3390\/cancers11010038"},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms12365","article-title":"Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis","volume":"7","author":"Konishi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1172\/JCI32205","article-title":"Microbial translocation augments the function of adoptively transferred self\/tumor-specific","volume":"117","author":"Paulos","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"4912","DOI":"10.4049\/jimmunol.1002046","article-title":"IL-18 oroduction downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation","volume":"185","author":"Zaki","year":"2010","journal-title":"J. Immunol."},{"key":"ref_339","doi-asserted-by":"crossref","unstructured":"Gupta, H., Youn, G.S., Shin, M.J., and Suk, K.T. (2019). Role of gut microbiota in hepatocarcinogenesis. Microorganisms, 7.","DOI":"10.20944\/preprints201903.0267.v1"},{"key":"ref_340","doi-asserted-by":"crossref","first-page":"e12525","DOI":"10.1111\/jpi.12525","article-title":"Melatonin and inflammation\u2014Story of a double-edged blade","volume":"65","author":"Hardeland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1159\/000447922","article-title":"Inhibition of ERK1\/2 signaling pathway is involved in melatonin\u2019s antiproliferative effect on human MG-63 osteosarcoma cells","volume":"39","author":"Liu","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-079X.2007.00509.x","article-title":"Epigenetic regulation: A new research area for melatonin?","volume":"44","author":"Korkmaz","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_343","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10549-008-0103-5","article-title":"Role of melatonin in the epigenetic regulation of breast cancer","volume":"115","author":"Korkmaz","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"9383","DOI":"10.3892\/mmr.2017.7836","article-title":"Melatonin inhibits colon cancer RKO cell migration by downregulating Rho-associated protein kinase expression via the p38\/MAPK signaling pathway","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_345","doi-asserted-by":"crossref","first-page":"e12586","DOI":"10.1111\/jpi.12586","article-title":"Epigenetic inhibition of the tumor suppressor ARHI by light at night-induced circadian melatonin disruption mediates STAT3-driven paclitaxel resistance in breast cancer","volume":"67","author":"Xiang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_346","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-079X.2008.00587.x","article-title":"Epigenetic targets for melatonin: Induction of histone H3 hyperacetylation and gene expression in C17.2 neural stem cells","volume":"45","author":"Sharma","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_347","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/er.2007-0012","article-title":"Nuclear receptor coregulators and human disease","volume":"28","author":"Lonard","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_348","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1600-079X.1995.tb00146.x","article-title":"Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer","volume":"18","author":"Molis","year":"1995","journal-title":"J. Pineal Res."},{"key":"ref_349","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.cdp.2007.10.018","article-title":"(-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells","volume":"31","author":"Farabegoli","year":"2007","journal-title":"Cancer Detect. Prev."},{"key":"ref_350","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-079X.2009.00729.x","article-title":"Sirtuins, melatonin and circadian rhythms: Building a bridge between aging and cancer","volume":"48","author":"Reiter","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_351","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jsbmb.2014.07.008","article-title":"Melatonin prevents neonatal dexamethasone induced programmed hypertension: Histone deacetylase inhibition","volume":"144","author":"Wu","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_352","doi-asserted-by":"crossref","first-page":"18484","DOI":"10.3390\/ijms151018484","article-title":"Transcriptional regulation of programmed hypertension by melatonin: An epigenetic perspective","volume":"15","author":"Tain","year":"2014","journal-title":"Int. J. Mol. Sci."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/2\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:18:11Z","timestamp":1760159891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/2\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":352,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["antiox10020210"],"URL":"https:\/\/doi.org\/10.3390\/antiox10020210","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]}}}