Lab. Tissue Engineering & Skin Pathophysiology, Dermatology Institute (Istituto Dermopatico dell'Immacolata, IDI IRCCS), Via Monti di Creta 104, Rome 00167, Italy.
Curr Med Chem. 2013;20(7):852-68.
As the incidence of skin tumors has been steadily growing, there is an urgent need for the preventive measures as well as the improved therapeutic approaches. In the last two decades, natural plant derived polyphenols (PPs, resveratrol, silibinin, green tea polyphenols, flavonoids, anthocyanins, etc.) have been drawing particular interest as emerging active substances in dermatological/cosmeceutical compositions for the prevention, slowing, or reversion of skin tumorigenesis (chemoprevention). When chronically applied to the skin, they supposedly would not damage normal skin cells or negatively affect their functions while they would suppress tumorigenic cell transformation, inhibit tumor cell proliferation, and activate tumor cell apoptosis. PPs are also reported to synergize with conventional anti-cancer therapies. The major aim of this critical review is to provide recent updates on the molecular and cellular targets for the prevention and therapy of skin tumors with a special focus on the crossroad between inflammation and carcinogenesis as the most promising approach to chemoprevention. Novel therapeutic targets as different as epidermal stem cells, cellular senescence, epigenetic enzymes involved in carcinogenesis, epidermal growth factor and aryl hydrocarbon receptors, and metabolic CYP1 subfamily enzymes are highlighted. The mechanisms of PPs interaction with these molecular and cellular targets are reviewed. The feasibility of PPs to prevent/ cure specific cutaneous toxicity connected to anti-EGFR therapy and to reduce multidrug resistance of skin tumors is also discussed.
随着皮肤肿瘤的发病率持续上升，人们迫切需要预防措施和改进的治疗方法。在过去的二十年中，天然植物来源的多酚（PPs，白藜芦醇、水飞蓟素、绿茶多酚、类黄酮、花青素等）作为皮肤科/化妆品组合物中新兴的活性物质，因其在预防、减缓或逆转皮肤肿瘤发生（化学预防）方面的作用而引起了特别关注。当它们被长期应用于皮肤时，据推测它们不会损伤正常皮肤细胞或对其功能产生负面影响，而会抑制致癌细胞转化、抑制肿瘤细胞增殖并激活肿瘤细胞凋亡。PPs 也被报道与传统的抗癌疗法具有协同作用。本综述的主要目的是提供有关皮肤肿瘤预防和治疗的最新分子和细胞靶点的最新信息，特别关注炎症和癌变之间的交叉点，这是化学预防最有前途的方法。强调了不同的新型治疗靶点，如表皮干细胞、细胞衰老、参与癌变的表观遗传酶、表皮生长因子和芳香烃受体以及代谢 CYP1 亚家族酶。综述了 PPs 与这些分子和细胞靶点相互作用的机制。还讨论了 PPs 预防/治疗与抗 EGFR 治疗相关的特定皮肤毒性和降低皮肤肿瘤的多药耐药性的可行性。
