{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:09:53Z","timestamp":1791043793078,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4001,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Fulbright Grant (to R.M.S.)"},{"name":"Spanish Ministry of Education, Culture & Sports (to R.M.S.)"},{"name":"FICYT (Fondo de Investigaci\u00f3n Cientifica y Desarrollo Tecnologico, Principado de Asturias, Spain) (post-doctoral fellowship to J.C.M.)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prostate"],"published-print":{"date-parts":[[2005,4,1]]},"DOI":"10.1002\/pros.20155","type":"journal-article","created":{"date-parts":[[2004,9,17]],"date-time":"2004-09-17T21:01:18Z","timestamp":1095454878000},"page":"29-43","source":"Crossref","is-referenced-by-count":136,"title":["Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism"],"prefix":"10.1002","volume":"63","author":[{"given":"Rosa M.","family":"Sainz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Mayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dun-xian","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"Le\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucien","family":"Manchester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,9,17]]},"reference":[{"key":"10.1002\/pros.20155-BIB1|cit1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/(SICI)1097-0045(19990501)39:2<135::AID-PROS9>3.0.CO;2-S","article-title":"Neuroendocrine differentiation in prostatic carcinoma","volume":"39","author":"Abrahamsson","year":"1999","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB2|cit2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3322\/canjclin.51.1.15","article-title":"Cancer Statistics, 2001","volume":"51","author":"Greenlee","year":"2001","journal-title":"CA Cancer J Clin"},{"key":"10.1002\/pros.20155-BIB3|cit3","first-page":"5030","article-title":"Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-steps process","volume":"59","author":"Craft","year":"1999","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB4|cit4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0090-4295(99)00452-5","article-title":"Chemotherapy for advanced hormone refractory prostate cancer","volume":"54","author":"Petrylak","year":"1999","journal-title":"Urology"},{"key":"10.1002\/pros.20155-BIB5|cit5","first-page":"5194","article-title":"Reversal of radiation resistance in LNCaP cells by targeting apoptosis through ceramide synthase","volume":"59","author":"Garzotto","year":"1999","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB6|cit6","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S0959-8049(96)00510-2","article-title":"Evolving strategies of cytotoxic chemotherapy for advanced prostate cancer","volume":"33","author":"Raghavan","year":"1997","journal-title":"Eur J Cancer"},{"key":"10.1002\/pros.20155-BIB7|cit7","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G","article-title":"Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer","volume":"28","author":"Denmeade","year":"1996","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB8|cit8","first-page":"4914","article-title":"Elevated expression of inhibitor of apoptosis proteins in prostate cancer","volume":"9","author":"Krajewska","year":"2003","journal-title":"Clin Cancer Res"},{"key":"10.1002\/pros.20155-BIB9|cit9","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3322\/canjclin.47.1.5","article-title":"Cancer statistics","volume":"47","author":"Parker","year":"1997","journal-title":"CA Cancer J Clin"},{"key":"10.1002\/pros.20155-BIB10|cit10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0009-8981(03)00048-2","article-title":"The role of nutrition in preventing prostate cancer: A review of proposed mechanism of action of various dietary substances","volume":"330","author":"Willis","year":"2003","journal-title":"Clin Chim Acta"},{"key":"10.1002\/pros.20155-BIB11|cit11","first-page":"247","volume-title":"Free radicals in aging","author":"Oberley","year":"1993"},{"key":"10.1002\/pros.20155-BIB12|cit12","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1080\/1071576021000038504","article-title":"Melatonin, longevity and health in the aged: An assessment","volume":"36","author":"Reiter","year":"2002","journal-title":"Free Radic Res"},{"key":"10.1002\/pros.20155-BIB13|cit13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568026023394443","article-title":"Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger","volume":"2","author":"Tan","year":"2002","journal-title":"Curr Top Med Chem"},{"key":"10.1002\/pros.20155-BIB14|cit14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/bies.950140307","article-title":"The aging pineal gland and its physiological consequences","volume":"14","author":"Reiter","year":"1992","journal-title":"Bioessays"},{"key":"10.1002\/pros.20155-BIB15|cit15","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1126\/science.7079745","article-title":"Decreased nocturnal plasma melatonin peaks in patients with estrogen receptor positive breast cancer","volume":"216","author":"Tamarkin","year":"1982","journal-title":"Science"},{"key":"10.1002\/pros.20155-BIB16|cit16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0009-8981(92)90164-L","article-title":"Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: Evidence for reduced pineal activity and relevance of urinary determinations","volume":"209","author":"Bartsch","year":"1992","journal-title":"Clin Chim Acta"},{"key":"10.1002\/pros.20155-BIB17|cit17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/(SICI)1097-0045(19980401)35:1<27::AID-PROS4>3.0.CO;2-E","article-title":"Melatonin receptors in benign prostate epithelial cells: Evidence for the involvements of cholera and pertussis toxins-sensitive G proteins in their signal transduction pathways","volume":"35","author":"Gilad","year":"1998","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB18|cit18","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0960-0760(98)00164-2","article-title":"Hormonal interactions in human prostate tumor LNCaP cells","volume":"68","author":"Lupowitz","year":"1999","journal-title":"J Steroid Biochem Mol Biol"},{"key":"10.1002\/pros.20155-BIB19|cit19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1600-079X.1999.tb00586.x","article-title":"Melatonin receptors in PC3 human prostate tumor cells","volume":"26","author":"Gilad","year":"1999","journal-title":"J Pineal Res"},{"key":"10.1002\/pros.20155-BIB20|cit20","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/1097-0045(200101)46:1<52::AID-PROS1008>3.0.CO;2-Z","article-title":"Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: Association of antiproliferative action of the pineal hormone with mt1 receptor protein expression","volume":"46","author":"Xi","year":"2001","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB21|cit21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/pros.1129","article-title":"Melatonin elicits nuclear exclusion of the human androgen receptor and attenuates its activity","volume":"49","author":"Rimler","year":"2001","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB22|cit22","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":"Montagnani Marelli","year":"2000","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB23|cit23","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1073\/pnas.91.12.5330","article-title":"Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP","volume":"91","author":"Bang","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/pros.20155-BIB24|cit24","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/S0022-5347(05)68241-9","article-title":"Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo","volume":"162","author":"Burchardt","year":"1999","journal-title":"J Urol"},{"key":"10.1002\/pros.20155-BIB25|cit25","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/sj.bjp.0705383","article-title":"Melatonin inhibits nitrate tolerance in isolated coronary arteries","volume":"139","author":"O'Rourke","year":"2003","journal-title":"Br J Pharmacol"},{"key":"10.1002\/pros.20155-BIB26|cit26","first-page":"902","article-title":"Luzindole (N-0774): A novel melatonin receptor antagonist","volume":"246","author":"Dubocovich","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1002\/pros.20155-BIB27|cit27","first-page":"50","article-title":"Melatonin receptors: Are there multiple subtypes?","volume":"16","author":"Dubocovich","year":"1995","journal-title":"TIPS"},{"key":"10.1002\/pros.20155-BIB28|cit28","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1096\/fasebj.12.12.1211","article-title":"Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms","volume":"12","author":"Dubocovich","year":"1998","journal-title":"FASEB J"},{"key":"10.1002\/pros.20155-BIB29|cit29","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/S0024-3205(03)00098-5","article-title":"Melatonin receptors and their regulation: Biochemical and structural mechanisms","volume":"72","author":"Witt-Enderby","year":"2003","journal-title":"Life Sci"},{"key":"10.1002\/pros.20155-BIB30|cit30","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0898-6568(01)00240-6","article-title":"Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and insensitive G proteins","volume":"14","author":"Chan","year":"2002","journal-title":"Cell Signal"},{"key":"10.1002\/pros.20155-BIB31|cit31","first-page":"3821","article-title":"Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: Implications for prostate cancer progression","volume":"59","author":"Cox","year":"1999","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB32|cit32","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.1038\/sj.onc.1204992","article-title":"Nuclear translocation of the catalytic subunit of protein kinase A induced by antisense oligonucleotide directed against the RI\u03b1 regulatory subunit","volume":"20","author":"Neary","year":"2001","journal-title":"Oncogene"},{"key":"10.1002\/pros.20155-BIB33|cit33","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/S0022-5347(17)32417-5","article-title":"The prostatic endocrine-paracrine (neuroendocrine) regulatory system and neuroendocrine differentiation in prostatic carcinoma: A review and future directions in basic research","volume":"152","author":"Di Sant'Agnese","year":"1994","journal-title":"J Urol"},{"key":"10.1002\/pros.20155-BIB34|cit34","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/1097-0142(19920701)70:1+<254::AID-CNCR2820701312>3.0.CO;2-E","article-title":"Neuroendocrine differentiation in prostatic carcinoma","volume":"1","author":"Di Sant'Agnese","year":"1992","journal-title":"Cancer"},{"key":"10.1002\/pros.20155-BIB35|cit35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/(SICI)1097-0045(1998)8+<43::AID-PROS8>3.0.CO;2-H","article-title":"Evaluation and clinical value of neuroendocrine differentiation in human prostatic tumors","volume":"8","author":"Cussenot","year":"1998","journal-title":"Prostate (Suppl)"},{"key":"10.1002\/pros.20155-BIB36|cit36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/(SICI)1097-0045(1996)6+<3::AID-PROS2>3.0.CO;2-T","article-title":"Neuroendocrine differentiation and hormone-refractory prostate cancer","volume":"6","author":"Abrahamsson","year":"1996","journal-title":"Prostate (Suppl)"},{"key":"10.1002\/pros.20155-BIB37|cit37","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1464-410X.1991.tb15318.x","article-title":"Neuro-endocrine cells: A new prognostic parameter in prostate cancer","volume":"68","author":"Cohen","year":"1991","journal-title":"Br J Urol"},{"key":"10.1002\/pros.20155-BIB38|cit38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/pros.2990240308","article-title":"A more objective staging of advanced prostate cancer-routine recognition of malignant endocrine structures: The assessment of serum TPS, PSA, and NSE values","volume":"24","author":"Tarle","year":"1994","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB39|cit39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0046-8177(95)90033-0","article-title":"Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells","volume":"26","author":"Bonkoff","year":"1995","journal-title":"Hum Pathol"},{"key":"10.1002\/pros.20155-BIB40|cit40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/03008880310006922","article-title":"Neuroendocrine differentiation in prostatic carcinoma","volume":"212","author":"Hamsson","year":"2003","journal-title":"Scand J Urol Nephrol (Suppl)"},{"key":"10.1002\/pros.20155-BIB41|cit41","first-page":"1967","article-title":"The androgen receptor status of neuroendocrine cells in human benign and malignant prostatic tissue","volume":"53","author":"Nakada","year":"1993","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB42|cit42","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1038\/sj.onc.1206764","article-title":"Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells","volume":"22","author":"Zhang","year":"2003","journal-title":"Oncogene"},{"key":"10.1002\/pros.20155-BIB43|cit43","doi-asserted-by":"crossref","first-page":"8471","DOI":"10.1128\/MCB.21.24.8471-8482.2001","article-title":"Interleukin-6 and cyclic AMP-mediated signaling potentiate neuroendocrine differentiation of LNCaP prostate tumor cells","volume":"21","author":"Deeble","year":"2001","journal-title":"Mol Cell Biol"},{"key":"10.1002\/pros.20155-BIB44|cit44","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0006-291X(03)00230-4","article-title":"Antioxidant activity of melatonin in Chinese hamster ovarian cells: Changes in cellular proliferation and differentiation","volume":"302","author":"Sainz","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/pros.20155-BIB45|cit45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1600-079X.2003.02112.x","article-title":"The chemistry of melatonin's interaction with reactive species","volume":"34","author":"Allegra","year":"2003","journal-title":"J Pineal Res"},{"key":"10.1002\/pros.20155-BIB46|cit46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1600-079X.2003.00092.x","article-title":"Regulation of antioxidant enzymes: A significant role for melatonin","volume":"36","author":"Rodriguez","year":"2004","journal-title":"J Pineal Res"},{"key":"10.1002\/pros.20155-BIB47|cit47","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1093\/jnci\/91.14.1227","article-title":"Effects of antioxidants on androgen-induced AP1 and NF\u03baB DNA-binding activity in prostate carcinoma cells","volume":"91","author":"Ripple","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"10.1002\/pros.20155-BIB48|cit48","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/jnci\/90.6.440","article-title":"Prostate cancer and supplementation with a-tocopherol and \u03b2-carotene: Incidence and mortality in a controlled trial","volume":"90","author":"Heinonen","year":"1998","journal-title":"J Natl Cancer Inst"},{"key":"10.1002\/pros.20155-BIB49|cit49","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1093\/jnci\/87.23.1767","article-title":"Intake of carotenoids and retinol in relation to risk of prostate cancer","volume":"87","author":"Giovannucci","year":"1995","journal-title":"J Natl Cancer Inst"},{"key":"10.1002\/pros.20155-BIB50|cit50","article-title":"Decreased incidence of prostate cancer with selenium (Se) supplementation: Results of a RCT [abstract]","author":"Clark","year":"1998","journal-title":"FEBS Proc"},{"key":"10.1002\/pros.20155-BIB51|cit51","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/(SICI)1097-0169(200005)46:1<28::AID-CM4>3.0.CO;2-5","article-title":"Melatonin induction of filamentous structures in non-neuronal cells that is dependent on expression of the human mt1 melatonin receptor","volume":"46","author":"Witt-Enderby","year":"2000","journal-title":"Cell Motil Cytoskeleton"},{"key":"10.1002\/pros.20155-BIB52|cit52","first-page":"6988","article-title":"Sinergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells","volume":"63","author":"Zu","year":"2003","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB53|cit53","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1073\/pnas.96.13.7490","article-title":"Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention","volume":"96","author":"Zi","year":"1999","journal-title":"PNAS"},{"key":"10.1002\/pros.20155-BIB54|cit54","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/pros.10219","article-title":"Growth inhibition and differentiation in human prostate carcinoma cells induced by the vitamin D analog 1a,24-dihydroxybitamin D2","volume":"55","author":"Bauer","year":"2003","journal-title":"Prostate"},{"key":"10.1002\/pros.20155-BIB55|cit55","first-page":"761","article-title":"Papaverine combined with prostaglandin E2 synergistically induces neuron-like morphological changes and decreases malignancy in human prostatic cancer LNCaP cells","volume":"20","author":"Shimizu","year":"2000","journal-title":"Anticancer Res"},{"key":"10.1002\/pros.20155-BIB56|cit56","doi-asserted-by":"crossref","first-page":"13812","DOI":"10.1074\/jbc.275.18.13812","article-title":"Activated 3\u2032,5\u2032-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrine-like differentiation of the LNCaP prostate tumor cell line","volume":"275","author":"Cox","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1002\/pros.20155-BIB57|cit57","first-page":"1549","article-title":"Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation","volume":"62","author":"Kim","year":"2002","journal-title":"Cancer Res"},{"key":"10.1002\/pros.20155-BIB58|cit58","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1210\/en.2002-221009","article-title":"Dual effect of pituitary adenylate cyclase activating polypeptide on prostate tumor LNCaP cells: Short and long-term exposure affect proliferation and neuroendocrine differentiation","volume":"144","author":"Farini","year":"2003","journal-title":"Endocrinology"},{"key":"10.1002\/pros.20155-BIB59|cit59","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1034\/j.1600-079X.2003.00074.x","article-title":"Melatonin slowed the early biochemical progression of hormone-refractory prostate cancer in patient whose prostate tumor tissue expressed MT1 receptor subtype","volume":"35","author":"Shiu","year":"2003","journal-title":"J Pineal Res"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.20155","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1002\/pros.20155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T04:25:10Z","timestamp":1625459110000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.20155"}},"subtitle":["Melatonin Induces Prostate Neuroendocrine Differentiation"],"short-title":[],"issued":{"date-parts":[[2004,9,17]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/pros.20155","archive":["Portico"],"relation":{},"ISSN":["0270-4137"],"issn-type":[{"value":"0270-4137","type":"print"}],"subject":[],"published":{"date-parts":[[2004,9,17]]}}}