Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma.
Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma.
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DOI：
10.1002/mnfr.201500822
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发表时间：
2016-06
影响因子：
5.2
通讯作者：
Meyskens FL
中科院分区：
文献类型：
--
作者：
Liu-Smith F;Meyskens FL
调味品正成为流行的营养品。不同的类黄酮对不同的组织或细胞类型显示出相似或不同的生物学效应，这可能限制或限定它们在癌症预防和/或治疗应用中的有用性。本文综述了几种黄酮类化合物，包括矢车菊素、芹菜素、染料木素、非瑟酮、表没食子儿茶素、毛地黄黄酮、黄芩素、槲皮素和山奈酚，并讨论了它们在正常和转化色素细胞中的功能。黄酮类化合物主要通过转录因子MiTF和/或黑素生成酶酪氨酸酶、DCT 2或TYRP-1表现出黑素生成或抗黑素生成作用。确定直接靶点一直是一个挑战，因为大多数研究无法区分类黄酮的作用是直接靶向还是间接作用。黄酮类化合物通过抑制黑色素瘤细胞的增殖、侵袭和诱导细胞凋亡而发挥抗黑色素瘤作用。其机制也是多方面的，通过ROS清除，免疫调节，细胞周期调节和表观遗传修饰，包括DNA甲基化和组蛋白去乙酰化。总之，虽然许多类黄酮化合物是非常有前途的营养保健品，但它们详细的分子机制和它们的多靶点（同时靶向多个分子）性质需要在进入翻译研究或临床试验之前进行进一步的研究。
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, DCT2 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 translation studies or clinical trials.