{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:33:29Z","timestamp":1791930809005,"version":"4.3.4"},"reference-count":250,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RMIT UNIVERSITY"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa\u2019s biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.<\/jats:p>","DOI":"10.3390\/ijms24010859","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:28:17Z","timestamp":1672806497000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8623-6289","authenticated-orcid":false,"given":"Ellen","family":"Schanknecht","sequence":"first","affiliation":[{"name":"The Pangenomics Lab, School of Science, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-2794","authenticated-orcid":false,"given":"Ava","family":"Bachari","sequence":"additional","affiliation":[{"name":"The Pangenomics Lab, School of Science, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazim","family":"Nassar","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0343-1781","authenticated-orcid":false,"given":"Terrence","family":"Piva","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-035X","authenticated-orcid":false,"given":"Nitin","family":"Mantri","sequence":"additional","affiliation":[{"name":"The Pangenomics Lab, School of Science, RMIT University, Bundoora, VIC 3083, Australia"},{"name":"UWA Institute of Agriculture, The University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1039\/c7pp00411g","article-title":"Melanoma\u2013role of the environment and genetics","volume":"17","author":"Cust","year":"2018","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1177\/1203475418773360","article-title":"Brief Report: Increase in Melanoma Incidence in Ontario","volume":"22","author":"Langley","year":"2018","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ypmed.2016.08.032","article-title":"Melanoma burden and recent trends among non-Hispanic whites aged 15\u201349 years, United States","volume":"91","author":"Watson","year":"2016","journal-title":"Prev. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/cncr.29258","article-title":"The past, present, and future of cancer incidence in the United States: 1975 through 2020","volume":"121","author":"Weir","year":"2015","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1038\/s41467-020-15546-9","article-title":"Pre-clinical modeling of cutaneous melanoma","volume":"11","author":"Rebecca","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jaad.2015.08.038","article-title":"Hereditary melanoma: Update on syndromes and management","volume":"74","author":"Soura","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jid.2016.01.035","article-title":"The Growing Burden of Invasive Melanoma: Projections of Incidence Rates and Numbers of New Cases in Six Susceptible Populations through 2031","volume":"136","author":"Whiteman","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"583748","DOI":"10.1155\/2010\/583748","article-title":"From Melanocyte to Metastatic Malignant Melanoma","volume":"2010","author":"Bandarchi","year":"2010","journal-title":"Dermatol. Res. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15003","DOI":"10.1038\/nrdp.2015.3","article-title":"Melanoma","volume":"1","author":"Schadendorf","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9280","DOI":"10.1038\/s41598-019-45643-9","article-title":"Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion","volume":"9","author":"Sarna","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","first-page":"65","article-title":"Choroidal melanoma resection. Middle East Afr","volume":"25","author":"Hamza","year":"2018","journal-title":"J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.annonc.2020.07.004","article-title":"ESMO consensus conference recommendations on the management of metastatic melanoma: Under the auspices of the ESMO Guidelines Committee","volume":"31","author":"Keilholz","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.canlet.2017.10.041","article-title":"Apigenin: A dietary flavonoid with diverse anticancer properties","volume":"413","author":"Gajski","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"106905","DOI":"10.1016\/j.intimp.2020.106905","article-title":"The therapeutic potential of resveratrol in a mouse model of melanoma lung metastasis","volume":"88","author":"Davoodvandi","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_16","unstructured":"Louis, B.W.-S. (2018). Cannabinoids and the entourage effect. Cannabis, Chapman and Hall\/CRC."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fnmol.2018.00487","article-title":"Cannabinoid Ligands Targeting TRP Channels","volume":"11","author":"Muller","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_18","first-page":"443","article-title":"Cannabinoids therapeutic use: What is our current understanding following the introduction of THC, THC: CBD oromucosal spray and others? Expert Rev","volume":"10","author":"Maccarrone","year":"2017","journal-title":"Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fphar.2017.00108","article-title":"Cannabis in Chinese medicine: Are some traditional indications referenced in ancient literature related to cannabinoids?","volume":"8","author":"Brand","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_20","unstructured":"Clarke, R., and Merlin, M. (2013). Ethnobotanical History and Contemporary Context of Medicinal Cannabis. Cannabis, University of California Press."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mechoulam, R. (2019). Cannabinoids as Therapeutic Agents, CRC Press.","DOI":"10.1201\/9780429260667"},{"key":"ref_22","first-page":"1311","article-title":"Phyto-, endo- and synthetic cannabinoids: Promising chemotherapeutic agents in the treatment of breast and prostate carcinomas. Expert Opin","volume":"25","year":"2016","journal-title":"Investig. Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nrc3247","article-title":"Towards the use of cannabinoids as antitumour agents","volume":"12","author":"Velasco","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3747\/co.23.3080","article-title":"Anticancer Mechanisms of Cannabinoids","volume":"23","author":"Velasco","year":"2016","journal-title":"Curr. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"172806","DOI":"10.1016\/j.ejphar.2019.172806","article-title":"\u03949-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor","volume":"865","author":"Darmani","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e016843","DOI":"10.1136\/bmjopen-2017-016843","article-title":"A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity","volume":"7","author":"Marinelli","year":"2017","journal-title":"BMJ Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.2147\/TCRM.S126849","article-title":"Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer","volume":"14","author":"Badowski","year":"2018","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1111\/j.1476-5381.2011.01621.x","article-title":"Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus","volume":"165","author":"Rock","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Silvestro, S., Mammana, S., Cavalli, E., Bramanti, P., and Mazzon, E. (2019). Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials. Molecules, 24.","DOI":"10.3390\/molecules24081459"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"974","DOI":"10.2174\/1570159X17666190603171901","article-title":"Cannabidiol Adverse Effects and Toxicity","volume":"17","author":"Huestis","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_31","first-page":"368","article-title":"Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany","volume":"64","year":"2021","journal-title":"Bundesgesundheitsblatt Gesundh. Gesundh."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Markovic, S.N., Erickson, L.A., Rao, R.D., McWilliams, R.R., Kottschade, L.A., Creagan, E.T., Weenig, R.H., Hand, J.L., Pittelkow, M.R., and Pockaj, B.A. (2007). Malignant melanoma in the 21st century, part 1: Epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clinic Proceedings, Elsevier.","DOI":"10.1016\/S0025-6196(11)61033-1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13046-018-0763-x","article-title":"Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma","volume":"37","author":"Huang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_34","first-page":"1452","article-title":"Clinical characteristics of malignant melanoma in central China and predictors of metastasis","volume":"19","author":"Shi","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.0303-6987.2006.00452.x","article-title":"The importance of mitotic rate as a prognostic factor for localized primary cutaneous melanoma","volume":"33","author":"Scolyer","year":"2006","journal-title":"J. Cutan. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/pcmr.12820","article-title":"Body site-specific genetic effects influence naevus count distribution in women","volume":"33","author":"Visconti","year":"2019","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1840415","DOI":"10.1155\/2020\/1840415","article-title":"Identification, Validation, and Functional Annotations of Genome-Wide Profile Variation between Melanocytic Nevus and Malignant Melanoma","volume":"2020","author":"Han","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Desai, A.D., Chinta, S., Yeh, C., Shah, V.P., Shah, R., Paskhover, B., and Schwartz, R.A. (2022). An analysis of lactate dehydrogenase (LDH) levels in advanced stage IV melanoma of the skin: Prognostic capabilities and demographic variability. Arch. Dermatol. Res., 1\u20138.","DOI":"10.21203\/rs.3.rs-1915668\/v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/bjd.18777","article-title":"The interplay of sun damage and genetic risk in Australian multiple and single primary melanoma cases and controls","volume":"183","author":"McMeniman","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_41","first-page":"1","article-title":"Epidemiology and Risk Factors of Melanoma","volume":"100","author":"Carr","year":"2019","journal-title":"Surg. Clin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1136\/adc.2005.086918","article-title":"Sun exposure and risk of melanoma","volume":"91","author":"Oliveria","year":"2005","journal-title":"Arch. Dis. Child."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/bjd.17833","article-title":"High naevus count and MC 1R red hair alleles contribute synergistically to increased melanoma risk","volume":"181","author":"Duffy","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12064","DOI":"10.1038\/ncomms12064","article-title":"Germline MC1R status influences somatic mutation burden in melanoma","volume":"7","author":"Espinoza","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ijc.24747","article-title":"Clinical whole-body skin examination reduces the incidence of thick melanomas","volume":"126","author":"Aitken","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.coi.2003.12.001","article-title":"NADPH oxidase","volume":"16","author":"Babior","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"ref_47","first-page":"206","article-title":"Antioxidant gene therapy against neuronal cell death","volume":"142","author":"Anandhan","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_48","first-page":"251","article-title":"Evaluation of anti-inflammatory property of melanin from marine Bacillus spp. BTCZ31","volume":"8","author":"Kurian","year":"2015","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/CMR.0000000000000612","article-title":"DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients","volume":"29","author":"Maric","year":"2019","journal-title":"Melanoma Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7234","DOI":"10.1158\/1078-0432.CCR-05-0683","article-title":"Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions","volume":"11","author":"Talantov","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e13270","DOI":"10.1111\/dth.13270","article-title":"BRAF V600E mutation as a prognostic factor in cutaneous melanoma patients","volume":"33","author":"Tas","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ejca.2016.12.012","article-title":"MAPK pathway in melanoma part II\u2014Secondary and adaptive resistance mechanisms to BRAF inhibition","volume":"73","author":"Amaral","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_53","first-page":"265","article-title":"Melanoma: Oncogenic drivers and the immune system","volume":"3","author":"Karachaliou","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e4757","DOI":"10.1136\/bmj.e4757","article-title":"Cutaneous melanoma attributable to sunbed use: Systematic review and meta-analysis","volume":"345","author":"Boniol","year":"2012","journal-title":"BMJ"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"501","DOI":"10.21873\/anticanres.13978","article-title":"Sunbeds and Melanoma Risk: Many Open Questions, Not Yet Time to Close the Debate","volume":"40","author":"Reichrath","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/j.ijwd.2017.02.003","article-title":"Cutaneous melanoma in women","volume":"3","author":"Roh","year":"2017","journal-title":"Int. J. Women\u2019s Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s12079-017-0419-1","article-title":"Why target the tumor stroma in melanoma?","volume":"12","author":"Hutchenreuther","year":"2017","journal-title":"J. Cell Commun. Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/CCO.0b013e3282f5271c","article-title":"The MAPK pathway in melanoma","volume":"20","author":"Fecher","year":"2008","journal-title":"Curr. Opin. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1158\/1541-7786.MCR-18-0327","article-title":"Hyperactivation of MAPK Signaling Is Deleterious to RAS\/RAF-mutant Melanoma","volume":"17","author":"Leung","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc969","article-title":"Targeting RAS signalling pathways in cancer therapy","volume":"3","author":"Downward","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40246-017-0109-3","article-title":"The NF1 somatic mutational landscape in sporadic human cancers","volume":"11","author":"Philpott","year":"2017","journal-title":"Hum. Genom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/978-1-4419-6448-9_13","article-title":"Familial Cutaneous Melanoma","volume":"Volume 685","author":"Hansson","year":"2010","journal-title":"Diseases of DNA Repair"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1177\/120347549800200312","article-title":"Role of the Cyclin-Dependent Kinase Inhibitor CDKN2A in Familial Melanoma","volume":"2","author":"Hogg","year":"1998","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.ejso.2016.10.005","article-title":"Diagnosis and treatment of in-transit melanoma metastases","volume":"43","author":"Testori","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10585-018-9893-y","article-title":"Genetics of metastasis: Melanoma and other cancers","volume":"35","author":"Turner","year":"2018","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"42601","DOI":"10.1038\/srep42601","article-title":"Risk of other Cancers in Families with Melanoma: Novel Familial Links","volume":"7","author":"Frank","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/ITT.S134842","article-title":"Melanoma treatment in review","volume":"7","author":"Domingues","year":"2018","journal-title":"Immuno Targets Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3322\/caac.21235","article-title":"Cancer treatment and survivorship statistics, 2014","volume":"64","author":"DeSantis","year":"2014","journal-title":"CA Cancer J. Clin."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1007\/s00264-020-04737-0","article-title":"Clinical characteristics, treatment, and prognosis of squamous cell carcinoma arising from extremity chronic osteomyelitis: A synthesis analysis of one hundred and seventy six reported cases","volume":"44","author":"Jiang","year":"2020","journal-title":"Int. Orthop."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1067\/msy.2003.141","article-title":"Increased surgical stress promotes tumor metastasis","volume":"133","author":"Tsuchiya","year":"2003","journal-title":"Surgery"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1158\/0008-5472.CAN-12-1993","article-title":"Preventing postoperative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells","volume":"73","author":"Tai","year":"2013","journal-title":"Cancer Res."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Inflammation","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kienzl, M., Kargl, J., and Schicho, R. (2020). The Immune Endocannabinoid System of the Tumor Microenvironment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238929"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/jb\/mvi021","article-title":"Endogenous Cannabinoid Receptor Ligand Induces the Migration of Human Natural Killer Cells","volume":"137","author":"Kishimoto","year":"2005","journal-title":"J. Biochem."},{"key":"ref_76","first-page":"1","article-title":"Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ejca.2009.10.032","article-title":"Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline","volume":"46","author":"Garbe","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0140-6736(12)60868-X","article-title":"Dabrafenib in BRAF-mutated metastatic melanoma: A multicentre, open-label, phase 3 randomised controlled trial","volume":"380","author":"Hauschild","year":"2012","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Blankenstein, S.A., Aarts, M.J.B., van den Berkmortel, F.W.P.J., Boers-Sonderen, M.J., van den Eertwegh, A.J.M., Franken, M.G., de Groot, J.W.B., Haanen, J.B.A.G., Hospers, G.A.P., and Kapiteijn, E. (2020). Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy. Cancers, 12.","DOI":"10.3390\/cancers12051176"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S1470-2045(18)30497-2","article-title":"Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): A multicentre, open-label, randomised, phase 3 trial","volume":"19","author":"Dummer","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S1470-2045(18)30142-6","article-title":"Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): A multicentre, open-label, randomised phase 3 trial","volume":"19","author":"Dummer","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1056\/NEJMoa1408868","article-title":"Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma","volume":"371","author":"Larkin","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/annonc\/mdx176","article-title":"Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E\/K-mutant melanoma: Long-term survival and safety analysis of a phase 3 study","volume":"28","author":"Long","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S0140-6736(13)60802-8","article-title":"Cutaneous melanoma","volume":"383","author":"Eggermont","year":"2014","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1203421","article-title":"Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma","volume":"367","author":"Flaherty","year":"2012","journal-title":"New Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2217\/fon.12.179","article-title":"Towards personalized therapy for patients with malignant melanoma: Molecular insights into the biology of BRAF mutations","volume":"9","author":"Bradish","year":"2013","journal-title":"Future Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1158\/1078-0432.CCR-16-1741","article-title":"Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1\/PD-L1Hyperprogressive Disease with Anti-PD-1\/PD-L1 Therapy","volume":"23","author":"Champiat","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2019.07.001","article-title":"Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: Long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial","volume":"119","author":"Eggermont","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e000491","DOI":"10.1136\/esmoopen-2019-000491","article-title":"Tolerability of BRAF\/MEK inhibitor combinations: Adverse event evaluation and management","volume":"4","author":"Heinzerling","year":"2019","journal-title":"ESMO Open"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41568-019-0154-4","article-title":"Phenotype plasticity as enabler of melanoma progression and therapy resistance","volume":"19","author":"Arozarena","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature08833","article-title":"RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth","volume":"464","author":"Hatzivassiliou","year":"2010","journal-title":"Nature"},{"key":"ref_93","first-page":"1","article-title":"Therapeutic potential of combined BRAF\/MEK blockade in BRAF-wild type preclinical tumor models","volume":"37","author":"Conciatori","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_94","first-page":"1","article-title":"Future prospects of immune checkpoint blockade in cancer: From response prediction to overcoming resistance","volume":"50","author":"Park","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cell.2015.03.030","article-title":"Immune Checkpoint Targeting in Cancer Therapy: Toward Combination Strategies with Curative Potential","volume":"161","author":"Sharma","year":"2015","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s40258-017-0341-y","article-title":"Estimated Healthcare Costs of Melanoma in Australia Over 3 Years Post-Diagnosis. Appl","volume":"15","author":"Elliott","year":"2017","journal-title":"Health Econ. Health Policy"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1200\/JCO.2017.74.1025","article-title":"Long-Term Outcomes in Patients With BRAF V600\u2013Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib","volume":"36","author":"Long","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"990","DOI":"10.3389\/fimmu.2019.00990","article-title":"Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma","volume":"10","author":"Yu","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ejca.2018.09.026","article-title":"Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort","volume":"105","author":"Kandel","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1056\/NEJMoa1414428","article-title":"Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma","volume":"372","author":"Postow","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-017-0458-3","article-title":"The use of immunotherapy in the treatment of melanoma","volume":"10","author":"Achkar","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/s41591-019-0476-5","article-title":"Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma","volume":"25","author":"Ribas","year":"2019","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41591-019-0474-7","article-title":"Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients","volume":"25","author":"Sullivan","year":"2019","journal-title":"Nat. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1200\/JCO.2018.36.5_suppl.189","article-title":"Preliminary findings from part 1 of COMBI-i: A phase III study of anti\u2013PD-1 antibody PDR001 combined with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600-mutant melanoma","volume":"36","author":"Dummer","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/pcmr.12383","article-title":"Severe gastrointestinal toxicity with administration of trametinib in combination with dabrafenib and ipilimumab","volume":"28","author":"Minor","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/1758834014566428","article-title":"Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma","volume":"7","author":"Welsh","year":"2015","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s12094-018-1891-7","article-title":"Cutaneous toxicities of new treatments for melanoma","volume":"20","author":"Boada","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1056\/NEJMoa1412690","article-title":"Improved overall survival in melanoma with combined dabrafenib and trametinib","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_111","first-page":"277","article-title":"Treatment and side effect management of CTLA-4 antibody therapy in metastatic melanoma","volume":"9","author":"Hauschild","year":"2010","journal-title":"JDDG J. Dtsch. Dermatol. Ges."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1038\/s41424-018-0049-9","article-title":"Immune Checkpoint Inhibitor-Associated Colitis and Hepatitis","volume":"9","author":"Reddy","year":"2018","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_113","first-page":"1","article-title":"Melanoma","volume":"1","author":"Schadendorf","year":"2015","journal-title":"Lancet"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.biopsych.2015.07.028","article-title":"An Introduction to the Endogenous Cannabinoid System","volume":"79","author":"Lu","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_115","first-page":"153","article-title":"Endocannabinoid system: An overview of its potential in current medical practice","volume":"30","author":"Mouslech","year":"2009","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Silver, R.J. (2019). The Endocannabinoid System of Animals. Animals, 9.","DOI":"10.20944\/preprints201906.0262.v1"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-21737-2_1","article-title":"Endocannabinoid System Components: Overview and Tissue Distribution","volume":"1162","author":"Joshi","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_118","first-page":"605","article-title":"Determination and characterization of a cannabinoid receptor in rat brain","volume":"34","author":"Devane","year":"1988","journal-title":"Mol. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fncel.2016.00294","article-title":"Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease","volume":"10","author":"Kendall","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jss.2018.08.055","article-title":"Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study in a Murine Model","volume":"235","author":"Simmerman","year":"2019","journal-title":"J. Surg. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/j.1476-5381.2011.01364.x","article-title":"Endocannabinoid tone versus constitutive activity of cannabinoid receptors","volume":"163","author":"Howlett","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1089\/can.2018.0039","article-title":"Cannabis systematics at the levels of family, genus, and species","volume":"3","author":"McPartland","year":"2018","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2307\/1220524","article-title":"A Practical and Natural Taxonomy for Cannabis","volume":"25","author":"Small","year":"1976","journal-title":"Taxon"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/can.2018.0063","article-title":"Cannabis Chemovar Nomenclature Misrepresents Chemical and Genetic Diversity; Survey of Variations in Chemical Profiles and Genetic Markers in Nevada Medical Cannabis Samples","volume":"5","author":"Speck","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s41232-018-0086-5","article-title":"Endocannabinoids and related N-acylethanolamines: Biological activities and metabolism","volume":"38","author":"Tsuboi","year":"2018","journal-title":"Inflamm. Regen."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11134","DOI":"10.1038\/s41598-020-68058-3","article-title":"A new role for anandamide: Defective link between the systemic and skin endocannabinoid systems in hypertrophic human wound healing","volume":"10","author":"Carvalho","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.3987\/COM-05-10501","article-title":"Isolation, synthesis and biological activity of grifolic acid dervivatives from the inedible mushroom Albatrellus dispansus","volume":"65","author":"Hashimoto","year":"2005","journal-title":"Heterocycles"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.tplants.2020.05.005","article-title":"Phytocannabinoids: Origins and Biosynthesis","volume":"25","year":"2020","journal-title":"Trends Plant Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1055\/s-0042-108058","article-title":"Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR","volume":"82","author":"Happyana","year":"2016","journal-title":"Planta Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/pros.23720","article-title":"Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits proliferation, migration, invasion, and tumor growth in prostate cancer in a cannabinoid-receptor 2 dependent manner","volume":"79","author":"Roberto","year":"2019","journal-title":"Prostate"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1089\/can.2018.0010","article-title":"Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression","volume":"3","author":"Nallathambi","year":"2018","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_133","first-page":"79","article-title":"Non-THC cannabinoids inhibit prostate carcinoma growthin vitroandin vivo: Pro-apoptotic effects and underlying mechanisms","volume":"168","author":"Ligresti","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ja01062a046","article-title":"Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish","volume":"86","author":"Gaoni","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1136\/adc.61.5.502","article-title":"Nabilone: An alternative antiemetic for cancer chemotherapy.. Arch","volume":"61","author":"Dalzell","year":"1986","journal-title":"Dis. Child."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/24740527.2022.2132138","article-title":"Synthetic cannabinoid for the treatment of severe chronic noncancer pain in children and adolescents","volume":"6","author":"Sun","year":"2022","journal-title":"Can. J. Pain"},{"key":"ref_137","unstructured":"Ho, C., and MacDougall, D. (2019). CADTH Rapid Response Reports. Nabilone for the Treatment of Nausea and Vomiting or Anorexia: A Review of Clinical Effectiveness and Guidelines, Canadian Agency for Drugs and Technologies in Health Copyright."},{"key":"ref_138","unstructured":"N.S.W. Health (2022, November 30). Cannabis Medicines Registered in Australia, Available online: https:\/\/www.medicinalcannabis.nsw.gov.au\/health-professionals\/product."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1373\/clinchem.2010.152439","article-title":"Plasma Cannabinoid Pharmacokinetics following Controlled Oral \u03949-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration","volume":"57","author":"Karschner","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bcp.2018.06.025","article-title":"Appraising the \u201centourage effect\u201d: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer","volume":"157","author":"Benito","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/jid.2015.45","article-title":"Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death","volume":"135","author":"Armstrong","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.lfs.2015.04.003","article-title":"Differential role of cannabinoids in the pathogenesis of skin cancer","volume":"138","author":"Glodde","year":"2015","journal-title":"Life Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1096\/fj.06-6638fje","article-title":"Cannabinoid receptors as novel targets for the treatment of melanoma","volume":"20","author":"Carracedo","year":"2006","journal-title":"FASEB J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/15321819.2020.1862863","article-title":"Effects of cannabidiol (CBD) on the inhibition of melanoma cells in vitro","volume":"42","author":"Burch","year":"2021","journal-title":"J. Immunoass. Immunochem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/BF02976895","article-title":"Synthesis and antitumor activity of cannabigerol","volume":"19","author":"Baek","year":"1996","journal-title":"Arch. Pharmacal Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.canlet.2011.07.008","article-title":"The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft","volume":"310","author":"Scuderi","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"8063","DOI":"10.3390\/ijms15058063","article-title":"CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier","volume":"15","author":"Fazakas","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s12253-012-9515-y","article-title":"Revisiting CB1 Receptor as Drug Target in Human Melanoma","volume":"18","author":"Kenessey","year":"2012","journal-title":"Pathol. Oncol. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejphar.2013.08.039","article-title":"Anticancer activity of anandamide in human cutaneous melanoma cells","volume":"718","author":"Adinolfi","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1471-2407-12-92","article-title":"The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action","volume":"12","author":"Hamtiaux","year":"2012","journal-title":"BMC Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/bjd.17333","article-title":"Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma","volume":"180","author":"Verykiou","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1097\/CAD.0000000000000246","article-title":"AM251 induces apoptosis and G2\/M cell cycle arrest in A375 human melanoma cells","volume":"26","author":"Carpi","year":"2015","journal-title":"Anti-Cancer Drugs"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbrc.2011.06.176","article-title":"\u03b1-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model","volume":"411","author":"Matsuo","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"114025","DOI":"10.1016\/j.bcp.2020.114025","article-title":"Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS","volume":"177","author":"Schomberg","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4877","DOI":"10.3892\/mmr.2020.11572","article-title":"Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM","volume":"22","author":"Woo","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"24011","DOI":"10.3390\/ijms161024011","article-title":"Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis","volume":"16","author":"Yang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"109984","DOI":"10.1016\/j.biopha.2020.109984","article-title":"Melanoma suppression by quercein is correlated with RIG-I and type I interferon signaling","volume":"125","author":"Peng","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11010-018-3296-x","article-title":"Quercetin exerts an inhibitory effect on cellular bioenergetics of the B164A5 murine melanoma cell line","volume":"447","author":"Sturza","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1080\/01635580701499545","article-title":"Quercetin Selectively Inhibits Bioreduction and Enhances Apoptosis in Melanoma Cells That Overexpress Tyrosinase","volume":"59","author":"Thangasamy","year":"2007","journal-title":"Nutr. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3390\/12051045","article-title":"Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells","volume":"12","author":"Kubo","year":"2007","journal-title":"Molecules"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"21731","DOI":"10.1038\/srep21731","article-title":"Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma","volume":"6","author":"Cao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"172568","DOI":"10.1016\/j.ejphar.2019.172568","article-title":"Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK\/P38 MAPK signaling activation","volume":"860","author":"Kim","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/adt.2020.993","article-title":"Quercetin Inhibits Proliferation and Induces Apoptosis of B16 Melanoma CellsIn Vitro","volume":"18","author":"Soll","year":"2020","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12943-015-0367-4","article-title":"Quercetin inhibits HGF\/c-Met signaling and HGF-stimulated melanoma cell migration and invasion","volume":"14","author":"Cao","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.18632\/oncotarget.26983","article-title":"The heterogeneity and complexity of Cannabis extracts as antitumor agents","volume":"10","author":"Baram","year":"2019","journal-title":"Oncotarget"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.tips.2016.04.005","article-title":"Beyond cannabis: Plants and the endocannabinoid system","volume":"37","author":"Russo","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_167","first-page":"335","article-title":"Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells. BMC Complement","volume":"16","author":"Lukhele","year":"2016","journal-title":"Altern. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fphar.2020.00359","article-title":"Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors","volume":"11","author":"Finlay","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Tomko, A.M., Whynot, E.G., Ellis, L.D., and Dupr\u00e9, D.J. (2020). Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis. Cancers, 12.","DOI":"10.3390\/cancers12071985"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/j.1476-5381.2010.01166.x","article-title":"Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes","volume":"163","author":"Ligresti","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/can.2019.0099","article-title":"Terpenoids Commonly Found in Cannabis sativa Do Not Modulate the Actions of Phytocannabinoids or Endocannabinoids on TRPA1 and TRPV1 Channels","volume":"5","author":"Heblinski","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Di Giacomo, S., Mariano, A., Gull\u00ec, M., Fraschetti, C., Vitalone, A., Filippi, A., Mannina, L., D\u2019Abusco, A.S., and Di Sotto, A. (2021). Role of Caryophyllane Sesquiterpenes in the Entourage Effect of Felina 32 Hemp Inflorescence Phytocomplex in Triple Negative MDA-MB-468 Breast Cancer Cells. Molecules, 26.","DOI":"10.3390\/molecules26216688"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.3389\/fpls.2018.01969","article-title":"The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No \u201cStrain,\u201d No Gain","volume":"9","author":"Russo","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fphar.2019.00430","article-title":"Modulation of the Endocannabinoid System as a Potential Anticancer Strategy","volume":"10","author":"Ramer","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.2147\/OTT.S106944","article-title":"Endocannabinoid system as a regulator of tumor cell malignancy\u2014biological pathways and clinical significance","volume":"9","author":"Pyszniak","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Perveen, S., and Al-Taweel, A. (2018). Terpenes and Terpenoids, Books on Demand.","DOI":"10.5772\/intechopen.71175"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1038\/s41598-020-60172-6","article-title":"Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots for Medicinal Purposes","volume":"10","author":"Jin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1055\/s-0043-122240","article-title":"Pharmacological Foundations of Cannabis Chemovars","volume":"84","author":"Lewis","year":"2018","journal-title":"Planta Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1080\/10942912.2016.1220393","article-title":"Natural polyphenols: An overview","volume":"20","author":"Abbas","year":"2017","journal-title":"Int. J. Food Prop."},{"key":"ref_181","unstructured":"Watson, R.R., Preedy, V.R., and Zibadi, S. (2018). Polyphenols: Prevention and Treatment of Human Disease, Academic Press."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.2741\/1595","article-title":"Synthetic peracetate tea polyphenols as potent proteasome inhibitors and apoptosis inducers in human cancer cells","volume":"10","author":"Deborah","year":"2005","journal-title":"Front. Biosci."},{"key":"ref_183","unstructured":"Bishop, K., Ferguson, L., and Braakhuis, A. (2018). Polyphenols for Cancer Treatment or Prevention, MDPI AG-Multidisciplinary Digital Publishing Institute."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"8526438","DOI":"10.1155\/2017\/8526438","article-title":"Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke","volume":"2017","author":"Cheng","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.2174\/1381612823666170329144307","article-title":"The relevance of dietary polyphenols in cardiovascular protection","volume":"23","author":"Murillo","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s40199-019-00289-w","article-title":"Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective","volume":"27","author":"Naseri","year":"2019","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbi.2017.11.022","article-title":"Chrysin, a natural and biologically active flavonoid suppresses tumor growth of mouse B16F10 melanoma cells: In vitro and In vivo study","volume":"283","author":"Sassi","year":"2018","journal-title":"Chem.-Biol. Interact."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5","article-title":"Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential","volume":"87","author":"Caltagirone","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2016.11.007","article-title":"Plant flavonoids in cancer chemoprevention: Role in genome stability","volume":"45","author":"George","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cofs.2016.01.009","article-title":"Anti-cancer efficacy of dietary polyphenols is mediated through epigenetic modifications","volume":"8","author":"Wu","year":"2016","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/obr.12409","article-title":"Effects of dietary polyphenols on metabolic syndrome features in humans: A systematic review","volume":"17","author":"Amiot","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.fct.2018.01.022","article-title":"Dietary polyphenols: Structures, bioavailability and protective effects against atherosclerosis","volume":"113","author":"Santhakumar","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Sharma, A., Shahzad, B., Rehman, A., Bhardwaj, R., Landi, M., and Zheng, B. (2019). Response of Phenylpropanoid Pathway and the Role of Polyphenols in Plants under Abiotic Stress. Molecules, 24.","DOI":"10.3390\/molecules24132452"},{"key":"ref_194","first-page":"60","article-title":"Biological activity of piceatannol: Leaving the shadow of resveratrol","volume":"750","author":"Piotrowska","year":"2012","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"109160","DOI":"10.1016\/j.biopha.2019.109160","article-title":"Pinosylvin reduced migration and invasion of oral cancer carcinoma by regulating matrix metalloproteinase-2 expression and extracellular signal-regulated kinase pathway","volume":"117","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"6791","DOI":"10.1021\/jf058050g","article-title":"Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin","volume":"53","author":"Castillo","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00011-009-0037-3","article-title":"Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease","volume":"58","author":"Villares","year":"2009","journal-title":"Inflamm. Res."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Liskova, A., Koklesova, L., Samec, M., Smejkal, K., Samuel, S.M., Varghese, E., Abotaleb, M., Biringer, K., Kudela, E., and Danko, J. (2020). Flavonoids in Cancer Metastasis. Cancers, 12.","DOI":"10.3390\/cancers12061498"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"24","DOI":"10.9734\/ejmp\/2020\/v31i1130296","article-title":"Characterization of Polyphenols, Flavonoids and Their Anti-microbial Activity in the Fruits of Vangueria madagascariensis JF Gmel","volume":"31","author":"Njenga","year":"2020","journal-title":"Eur. J. Med. Plants"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2174\/1568026616666160927160620","article-title":"Hybrid Compounds as Direct Multitarget Ligands: A Review","volume":"17","author":"Pedrosa","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s00403-017-1784-6","article-title":"Resveratrol suppresses melanoma by inhibiting NF-\u03baB\/miR-221 and inducing TFG expression","volume":"309","author":"Wu","year":"2017","journal-title":"Arch. Dermatol. Res."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Abotaleb, M., Samuel, S.M., Varghese, E., Varghese, S., Kubatka, P., Liskova, A., and B\u00fcsselberg, D. (2018). Flavonoids in Cancer and Apoptosis. Cancers, 11.","DOI":"10.3390\/cancers11010028"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1080\/10408398.2015.1074532","article-title":"Natural and Synthetic Flavonoids: Structure\u2013Activity Relationship and Chemotherapeutic Potential for the Treatment of Leukemia","volume":"56","author":"Menezes","year":"2015","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"3128951","DOI":"10.1155\/2016\/3128951","article-title":"Role of Natural Stilbenes in the Prevention of Cancer","volume":"2016","author":"Sirerol","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jinorgbio.2013.07.038","article-title":"Effects of chrysin, apigenin, genistein and their homoleptic copper (II) complexes on the growth and metastatic potential of cancer cells","volume":"127","author":"Spoerlein","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.toxlet.2015.01.008","article-title":"Chemopreventive and therapeutic potential of chrysin in cancer: Mechanistic perspectives","volume":"233","author":"Kasala","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"9413","DOI":"10.1021\/acs.jmedchem.6b01026","article-title":"Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy","volume":"60","author":"Estrela","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/ptr.5061","article-title":"Quercetin and EGCG Exhibit Chemopreventive Effects in Cholangiocarcinoma Cells via Suppression of JAK\/STAT Signaling Pathway","volume":"28","author":"Senggunprai","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00394-015-0854-9","article-title":"The combination of resveratrol and quercetin enhances the individual effects of these molecules on triacylglycerol metabolism in white adipose tissue","volume":"55","author":"Arias","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/00498254.2011.609570","article-title":"Natural prenylated resveratrol analogs arachidin-1 and -3 demonstrate improved glucuronidation profiles and have affinity for cannabinoid receptors","volume":"42","author":"Brents","year":"2011","journal-title":"Xenobiotica"},{"key":"ref_212","first-page":"4025","article-title":"Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin","volume":"29","author":"Hsieh","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"104712","DOI":"10.1016\/j.fitote.2020.104712","article-title":"Cannflavins\u2013From plant to patient: A scoping review","volume":"146","author":"Erridge","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/BF02118655","article-title":"Cannflavin A and B, prenylated flavones from Cannabis sativa L","volume":"42","author":"Barrett","year":"1986","journal-title":"Experientia"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/0006-2952(85)90325-9","article-title":"Isolation from Cannabis sativa L. of cannflavin\u2014A novel inhibitor of prostaglandin production","volume":"34","author":"Barrett","year":"1985","journal-title":"Biochem Pharmacol."},{"key":"ref_216","unstructured":"Seegers, J. (2014). Identification and Characterization of Natural Products as Dual Inhibitors of Microsomal Prostaglandin E2 Synthase-1 and 5-Lipoxygenase. [Ph.D. Thesis, Universit\u00e4t T\u00fcbingen]."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.phanu.2014.05.001","article-title":"Cannflavins from hemp sprouts, a novel cannabinoid-free hemp food product, target microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase","volume":"2","author":"Werz","year":"2014","journal-title":"PharmaNutrition"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/pcmr.12455","article-title":"Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression","volume":"29","author":"Kim","year":"2016","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jnutbio.2008.03.005","article-title":"Apigenin causes G2\/M arrest associated with the modulation of p21Cip1 and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells","volume":"20","author":"Choi","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11010-012-1310-2","article-title":"Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NF\u03baB signaling in HER2-overexpressing breast cancer cells","volume":"366","author":"Seo","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/j.freeradbiomed.2008.02.007","article-title":"Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation","volume":"44","author":"Shukla","year":"2008","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/mc.22005","article-title":"Apigenin inhibits TGF-\u03b2-induced VEGF expression in human prostate carcinoma cells via a Smad2\/3-and Src-dependent mechanism","volume":"53","author":"Mirzoeva","year":"2014","journal-title":"Mol. Carcinog."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"817674","DOI":"10.1155\/2013\/817674","article-title":"Subtoxic levels of apigenin inhibit expression and secretion of VEGF by uveal melanoma cells via suppression of ERK1\/2 and PI3K\/Akt pathways","volume":"2013","author":"Chao","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.plefa.2015.11.006","article-title":"Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice","volume":"104","author":"Kiraly","year":"2015","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13578-017-0179-x","article-title":"Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action","volume":"7","author":"Yan","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"9358","DOI":"10.1021\/acs.jafc.0c03123","article-title":"Chrysin Inhibits Melanoma Tumor Metastasis via Interfering with the FOXM1\/\u03b2-Catenin Signaling","volume":"68","author":"Yufei","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1248\/bpb.b17-00892","article-title":"Biochemical Characterization of Ferulic Acid and Caffeic Acid Which Effectively Inhibit Melanin Synthesis via Different Mechanisms in B16 Melanoma Cells","volume":"41","author":"Maruyama","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11418-017-1120-7","article-title":"Whitening and anti-wrinkle activities of ferulic acid isolated from Tetragonia tetragonioides in B16F10 melanoma and CCD-986sk fibroblast cells","volume":"72","author":"Park","year":"2018","journal-title":"J. Nat. Med."},{"key":"ref_229","first-page":"132","article-title":"A recent overview on the biological and pharmacological activities of ferulic acid","volume":"18","author":"Kim","year":"2019","journal-title":"Excli J."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"9293416","DOI":"10.1155\/2019\/9293416","article-title":"2-Methoxyestradiol and its combination with a natural compound, ferulic acid, induces melanoma cell death via downregulation of Hsp60 and Hsp90","volume":"2019","author":"Kamm","year":"2019","journal-title":"J. Oncol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.btre.2014.09.002","article-title":"Potential applications of ferulic acid from natural sources","volume":"4","author":"Kumar","year":"2014","journal-title":"Biotechnol. Rep."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-019-1292-y","article-title":"Role of protein kinase CK2 in antitumor drug resistance","volume":"38","author":"Borgo","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3746\/pnf.2015.20.1.73","article-title":"Differential effects of methoxylated p-coumaric acids on melanoma in B16\/F10 cells","volume":"20","author":"Yoon","year":"2015","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"21674","DOI":"10.18632\/oncotarget.15535","article-title":"Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK\/paxillin and MAPK pathways","volume":"8","author":"Cui","year":"2017","journal-title":"Oncotarget"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.intimp.2018.06.009","article-title":"Genistein reduces proliferation of EP3-expressing melanoma cells through inhibition of PGE2-induced IL-8 expression","volume":"62","author":"Venza","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1039\/C8FO02013B","article-title":"Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K\/AKT pathway","volume":"10","author":"Yao","year":"2019","journal-title":"Food Funct."},{"key":"ref_237","first-page":"5349","article-title":"Methyl p-coumarate, a melanin formation inhibitor in B16 mouse melanoma cells. Bioorganic Med","volume":"12","author":"Kubo","year":"2004","journal-title":"Chem."},{"key":"ref_238","first-page":"579","article-title":"Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation","volume":"110","author":"Shen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.biopha.2018.02.035","article-title":"Molecular chemoprevention by morin\u2014A plant flavonoid that targets nuclear factor kappa B in experimental colon cancer","volume":"100","author":"Sharma","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"112922","DOI":"10.1016\/j.jpba.2019.112922","article-title":"Effect of light, oxygen and temperature on the stability of artepillin C and p-coumaric acid from Brazilian green propolis","volume":"178","author":"Arruda","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_241","first-page":"659","article-title":"Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.. Clin","volume":"2","author":"Ferry","year":"1996","journal-title":"Cancer Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.clnu.2013.08.011","article-title":"Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model","volume":"33","author":"Sharmila","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"117463","DOI":"10.1016\/j.lfs.2020.117463","article-title":"A review on anti-cancer properties of Quercetin in breast cancer","volume":"248","author":"Ezzati","year":"2020","journal-title":"Life Sci."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Hundsberger, H., Stierschneider, A., Sarne, V., Ripper, D., Schimon, J., Weitzenb\u00f6ck, H., Schild, D., Jacobi, N., Eger, A., and Atzler, J. (2021). Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models. Molecules, 26.","DOI":"10.3390\/molecules26030717"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3923\/jbs.2007.1511.1519","article-title":"Antiangiogenic effect of rutin and its regulatory effect on the production of VEGF, IL-1\u03b2 and TNF-\u03b1 in tumor associated macrophages","volume":"7","author":"Guruvayoorappan","year":"2007","journal-title":"J. Biol. Sci."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0304-3835(95)03887-3","article-title":"Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds","volume":"95","author":"Menon","year":"1995","journal-title":"Cancer Lett."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2174\/1389201019666180209165523","article-title":"Rutin and Its Cyclodextrin Inclusion Complexes: Physico-chemical Evaluation and in vitro Activity on B164A5 Murine Melanoma Cell Line","volume":"18","author":"Corina","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/j.freeradbiomed.2018.10.125","article-title":"Targeting protein disulfide isomerase to overcome resistance to BRAF inhibitors in melanoma","volume":"128","author":"Beyerstedt","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.phrs.2009.01.017","article-title":"Natural compounds for cancer treatment and prevention","volume":"59","author":"Nobili","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_250","first-page":"362","article-title":"Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays. SLAS Discov","volume":"24","author":"Otvos","year":"2019","journal-title":"Adv. Sci. Drug Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:57:34Z","timestamp":1760119054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,3]]},"references-count":250,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010859"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010859","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,3]]}}}