Clinical and laboratory studies have demonstrated that skin exposure to ultraviolet radiation (UV) is the main cause of non-melanoma skin cancer (NMSC) (≈ 99%) and melanoma (≈ 95%) development. The procarcinogenic effects of solar exposure are mainly due to UVB radiation (290-320 nm range), the same tight range that produces burning in human skin (erythema), inflammation, oxidative stress, DNA damage, etc. The number of skin cancers around the world keeps increasing and, thus, it is an urgent need to find effective protection remedies. Phytoalexins of polyphenolic structure are naturally occurring compounds involved in the defense against pathogens and environmental stresses in plants. Epidemiological studies confirm that diets enriched in plant polyphenols may offer protection against chronic diseases related to oxidative stress. In this sense polyphenols have shown anticarcinogenic and photoprotective effects (e.g. Clifford JL & DiGiovanni J. Cancer Prev Res 3:132-5, 2010). Seminal studies showed that resveratrol (trans-3,5,4′-trihydroxystilbene; Resv) exerted chemopreventive activity in a model of mouse skin carcinogenesis where topic administration of this polyphenol inhibited multistage carcinogenesis [Jang M et al. Science 275:218-20, 1997]. Pterostilbene (3,5-dimethoxy-4′-hydroxy-trans-stilbene; Pter), a Res analog, shows a higher half-life and more potent anticancer effects in vivo than Res. We compared the potential anti-UVB protection of both polyphenols in a murine model of chronic irradiation (180 mJ UVB/cm2; 3 doses/week; for a total of 30 weeks) that experimentally resembles long-term chronic human exposure to damaging sun radiations. We observed that topical pretreatment of the skin with Pter (1-2 μmol/cm2 per dose, administered right before UB exposure), but not with Resv, fully prevents chronic UVB-induced skin carcinogenesis. The molecular mechanism underlying this protective effect involves a Pter-induced increase in antioxidant skin defenses and a decrease in the rate of mutagenesis.

Citation Format: J. Antoni Sirerol, Ines Pulido, Miguel Asensi, Angel Ortega, Jose M. Estrela. Pterostilbene, a natural phytoalexin, effectively protects against UVB-induced skin carcinogenesis by increasing antioxidant cellular defenses and preventing mutagenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1605. doi:10.1158/1538-7445.AM2014-1605