Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in survivin

Abstract

Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV-B component, 290-320 nm), is its major cause. 'Chemoprevention' by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans-3, 5, 4-trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV-B-mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of resveratrol-mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV-exposure-mediated modulations in (1) cki-cyclin-cdk network, and (2) mitogen activated protein kinase (MAPK)-pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family Survivin during resveratrol-mediated protection from multiple exposures of UV-B (180 mJ/cm(2); on alternate days; for a total of seven exposures) radiations in the SKH-1 hairless mouse skin. Our data demonstrated that topical pre-treatment of resveratrol (10 micromol in 200 microl acetone/mouse) resulted in significant inhibition of UV-B exposure-mediated increases in (1) cellular proliferations (Ki-67 immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B-mediated decrease of Smac/DIABLO, and (2) enhancement of UV-B-mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV-B exposure-mediated damages in SKH-1 hairless mouse skin via inhibiting Survivin and the associated events.