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

Photochem Photobiol. Jan-Feb 2005;81(1):25-31. doi: 10.1562/2004-08-13-RA-274.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Female
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Hairless
  • Microtubule-Associated Proteins / physiology*
  • Repressor Proteins
  • Resveratrol
  • Skin / drug effects*
  • Skin / radiation effects*
  • Stilbenes / pharmacology*
  • Survivin
  • Ultraviolet Rays*

Substances

  • Birc5 protein, mouse
  • DNA Primers
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Repressor Proteins
  • Stilbenes
  • Survivin
  • Resveratrol