Abstract 4239: Pterostilbene, a natural polyphenol, elicits full protection against ultraviolet B radiation-induced skin carcinogenesis: Preclinical studies

Abstract

Solar radiation exposure is the chief cause of nonmelanoma (i e, basal cell and squamous cell) skin cancer, and it is also a prime factor in the etiology of cutaneous melanoma The cancer-causing effects of ultraviolet (UV) radiation on the skin are mainly produced by UV-B radiation in the 290- to 320-nm range, the same range that produces burning in human skin (erythema) UV-B exposure can damage DNA and be immunosuppressive Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of effective protection from UV radiation Resveratrol (trans-3,5,4′-trihydroxystilbene; RES) is a phytoalexin present in a wide variety of plant species, where its synthesis is induced by stress conditions The cancer chemopreventive activity of RES was first reported by Jang et al [Science 275, 218 – 220 (1997)] in a model of skin carcinogenesis where topic administration of this polyphenol inhibited multistage mouse skin carcinogenesis Equally promising action is exerted by resveratrol analogues, mainly pterostilbene (3,5-dimethoxy-4′-hydroxy-trans-stilbene: PTER), which shows a higher half-life in vivo and more potent anticancer effects in vivo than RES Our aim was to compare the anticancer effects of RES and PTER in UVB-induced mouse skin carcinogenesis In our experiments, Female SKH-1 hairless mice were irradiated with UVB (180 mJ/cm2; 3 doses/week; for a total of 30 weeks) 20 min after or before the topical administration of liposomes containing a total of 10 μmol of RES or PTER/mice (aprox 2 5 μmol/cm2 of skin) This long-term UVB administration reproduces, in an animal model, which are the consequences in humans of receiving chronic UVB radiations We observed that pretreatment of the skin with PTER resulted in a dramatic reduction in UVB-induced skin tumorigenesis (90 % of tumor free-mice at the end of treatment, n=20; P<0 01), whereas all RES-treated mice showed carcinomas (0 % of tumor free-mice on the 30th week, n=20) Molecular mechanisms involved in this strong anticancer effect elicited by Pter (as compared with RES) suggest differences in prevention of DNA mutagenesis, and protein and lipid oxidation Our results indicate that PTER can be used efficiently in the prevention of skin carcinogenesis induced by solar radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4239. doi:10.1158/1538-7445.AM2011-4239