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RESEARCH PRODUCT

Abstract 1280: Pterostilbene exerts full protection against UVB-induced skin carcinogenesis.

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Abstract Epidemiological, clinical and laboratory studies have demonstrated that solar ultraviolet (UV) radiation is the main cause of nonmelanoma skin cancer (i.e., basal cell and squamous cell carcinoma) and it is also a prime factor in the etiology of cutaneous melanoma. The cancer-causing effects of solar exposure 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), inflammation, oxidative stress, DNA damage, etc. Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of an effective protection against UV radiation. Polyphenols (PFs) are abundant in many fruits and vegetables, wine, tea, and various dietary supplements. The role of these natural molecules as potential anticarcinogens and photoprotectors has been postulated (e.g. Clifford JL & DiGiovanni J. Cancer Prev Res 3: 132-5, 2010). 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-transstilbene: PTER), which shows a higher half-life and more potent anticancer effects in vivo than RES. The long-term UV-B administration (180 mJ/cm2; 3 doses/week; for a total of 30 weeks) reproduces, in an animal model, which are the consequences in humans of receiving chronic UV-B radiations. We observed that pretreatment of the skin with PTER prevented UV-B-induced skin tumorigenesis (∼90 % of tumor free-mice at the end of treatment, n=20; P<0.01). Our aim was to study the key molecular mechanisms involved in this strong anticancer effect elicited by PTER. Our results indicate that PTER efficiently avoid skin carcinogenesis induced by solar radiation by decreasing DNA mutagenesis, and protein and lipid oxidation. Citation Format: Angel Ortega, Maria L. Rodriguez, Joan A. Sirerol, Ines Pulido, Daniel Crespo, Julian Carretero, Miguel A. Asensi, Salvador Mena, Jose M. Estrela. Pterostilbene exerts full protection against UVB-induced skin carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1280. doi:10.1158/1538-7445.AM2013-1280