Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>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 (<jats:italic>trans</jats:italic>‐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 (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b1">1</jats:ext-link>) cki‐cyclin‐cdk network and (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b2">2</jats:ext-link>) mitogen activated protein kinase (MAPK)‐pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family protein Survivin during resveratrol‐mediated protection from multiple exposures of UV‐B (180 mJ/cm<jats:sup>2</jats:sup>; on alternate days; for a total of seven exposures) radiations in the SKH‐1 hairless mouse skin. Our data demonstrated that topical pretreatment of resveratrol (10 μmol in 200 μL acetone/mouse) resulted in significant inhibition of UV‐B exposure‐mediated increases in (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b1">1</jats:ext-link>) cellular proliferations (Ki‐67 immunostaining), (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b2">2</jats:ext-link>) protein levels of epidermal cyclooxygenase‐2 and ornithine decarboxylase, established markers of tumor promotion, (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b3">3</jats:ext-link>) protein and messenger RNA levels of Survivin, and (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b4">4</jats:ext-link>) phosphorylation of survivin in the skin of SKH‐1 hairless mouse. Resveratrol pretreatment also resulted in (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b1">1</jats:ext-link>) reversal of UV‐B–mediated decrease of Smac/DIABLO and (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b2">2</jats:ext-link>) 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.</jats:p>