title: Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma.
abstract: Flavonoids are becoming popular nutraceuticals. Different flavonoids show similar or distinct biological effects on different tissues or cell types, which may limit or define their usefulness in cancer prevention and/or treatment application. This review focuses on a few selected flavonoids and discusses their functions in normal and transformed pigment cells, including cyanidin, apigenin, genistein, fisetin, EGCG, luteolin, baicalein, quercetin and kaempferol. Flavonoids exhibit melanogenic or anti-melanogenic effects mainly via transcriptional factor MiTF and/or the melanogenesis enzymes tyrosinase, DCT or TYRP-1. To identify a direct target has been a challenge as most studies were not able to discriminate whether the effect(s) of the flavonoid were from direct targeting or represented indirect effects. Flavonoids exhibit an anti-melanoma effect via inhibiting cell proliferation and invasion and inducing apoptosis. The mechanisms are also multi-fold, via ROS-scavenging, immune-modulation, cell cycle regulation and epigenetic modification including DNA methylation and histone deacetylation. In summary, although many flavonoid compounds are extremely promising nutraceuticals, their detailed molecular mechanism and their multi-target (simultaneously targeting multiple molecules) nature warrant further investigation before advancement to translational studies or clinical trials.
authors: Department of Epidemiology, UC Irvine, Irvine, CA, USA.|Department of Medicine, UC Irvine, Irvine, CA, USA.|Department of Public Health, UC Irvine, Irvine, CA, USA.
authors: Feng
authors: F
authors: Liu-Smith
authors: Department of Epidemiology, UC Irvine, Irvine, CA, USA.|Department of Medicine, UC Irvine, Irvine, CA, USA.|Department of Public Health, UC Irvine, Irvine, CA, USA.|Department of Biological Chemistry, UC Irvine, Irvine, CA, USA.|Chao Family Comprehensive Cancer Center, UC Irvine, Irvine, CA, USA.
authors: Frank L
authors: FL
authors: Meyskens
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D029382:Dicarboxylic Acid Transporters / Q000378:metabolism; D044127:Epigenesis, Genetic; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000188:drug therapy* / Q000517:prevention & control*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D029382:Dicarboxylic Acid Transporters; D005419:Flavonoids; D008543:Melanins; D017382:Reactive Oxygen Species; D014442:Monophenol Monooxygenase
keywords: Flavonoids; Luteolin; Melanogenesis; Melanoma; Prevention