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Because resveratrol has strong antioxidant properties, and oxidative stress is believed to be a critical factor in a variety of cutaneous conditions including skin cancers, a number of in vitro studies have been done to determine the anti-proliferative effects as well as photo-protective effects of resveratrol. Some of these in vitro studies. In two studies from this laboratory, we demonstrated that resveratrol, via modulating cyclin kinase inhibitor (cki)-cyclin-cyclin dependent kinase (cdk) network and retinoblastoma (pRb)-E2F/DP machinery, resulted in a G1-phase arrest of the cell cycle and apoptosis of human epidermoid carcinoma (A431) cells.
Another in vitro study demonstrated that resveratrol was able to induce apoptosis in two human melanoma cell lines. Yang and colleagues showed that resveratrol inhibits APE/Ref-1 and significantly decreases AP-1/JunD, MMP-1, Bcl-2, and iNOS protein levels in melanoma cells. Since, in this study, nitric oxide was found to initiate progression of human melanoma via a feedback loop mediated by apurinic/apyrimidinic endonuclease-1/redox factor-1, the authors suggested that resveratrol could be an appropriate choice for combining with other compounds that develop resistance by up-regulation of these molecules.
This group also demonstrated that that resveratrol inhibited anchorage-independent growth of melanoma cell lines. Further, the authors also noted that following treatment with resveratrol, the cells appeared to act more “normal”, as if resveratrol had caused the cells to differentiate. Resveratrol did not have any cytotoxic effects on the lines tested, but did change the morphology of the cells, as well as elevate the MHC class I antigen and Fas expression levels, and decreased AP-1 binding and transcriptional activities. It was also found that resveratrol decreased intracellular reactive oxygen species in melanoma cells. In another study, Osmond and colleagues showed that resveratrol significantly decreased the viability of melanoma cell lines (DM738 and DM443) without similar effects in fibroblast cells. Further, resveratrol significantly enhanced the cytotoxicity of temozolomide in melanoma cells.
In an in vitro study, we have also shown that resveratrol treatment blocked UVB-mediated activation of NF-κB pathway in the normal human epidermal keratinocytes (NHEK), in a dose- as well as time- dependent fashion. In a study done by Liu and colleagues, it was shown that resveratrol protects human HaCaT keratinocytes from UVA-induced oxidative stress damage by downregulating Keap1 expression. Recently, in another study it was found that there are specific polyphenol receptor sites in the skin that bind resveratrol, which then exert protective effects against the nitric oxide free radical donor sodium nitroprusside (SNP). To determine the receptor binding, the authors treated human skin tissue sections with [3H]-resveratrol followed by studying localization of signals. A significant binding of resveratrol was seen in the epidermis, with some binding in the dermis. The study also determined that the resveratrol binding site was also present in vitro, in HaCaT cells, an immortalized human keratinocyte cell line. This study gives promise to the notion that skin diseases and cancers can be treated with resveratrol because of the resveratrol-specific binding sites in the skin.
Article Produced By
Department of Dermatology, University of Wisconsin, University of Wisconsin Carbone Cancer Center, Corresponding author: Nihal Ahmad, Medical Sciences Center,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060966/
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