Flavonoid antioxidant silymarin and skin cancer.
Oxidative stress is one of the key players in skin carcinogenesis, and therefore identifying nontoxic strong antioxidants to prevent skin cancer is an important area of research. In both animal and cell culture studies, we have shown that silymarin, a naturally occurring polyphenolic flavonoid antioxidant, exhibits preventive and anticancer effects against skin cancer. For example, silymarin strongly prevents both photocarcinogenesis and skin tumor promotion in mice, in part, by scavenging free radicals and reactive oxygen species and strengthening the antioxidant system. We also found that this effect of silymarin is by inhibiting endogenous tumor promoter tumor necrosis factor alpha in mouse skin, a central mediator in skin tumor promotion. In mechanistic studies, silymarin inhibits mitogenic and cell survival signaling and induces apoptosis. Furthermore, silymarin effectively modulates cell-cycle regulators and check points toward inhibition of proliferation, and growth arrest in G0-G1 and G2-M phases of the cell cycle. Thus, due to its mechanism-based chemopreventive and anticancer effects in experimental models, silymarin is an important candidate for the prevention and/or therapy of skin cancer, as well as other cancers of epithelial origin in humans.
Singh
Rana P
RP
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Agarwal
Rajesh
R
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D015394:Molecular Structure; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012838:Silymarin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
D000975:Antioxidants; D007375:Interleukin-1; D020011:Protective Agents; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D008084:Lipoxygenase; D003576:Electron Transport Complex IV