Cancer chemopreventive activity of resveratrol

Ann N Y Acad Sci. 2002 May:957:210-29. doi: 10.1111/j.1749-6632.2002.tb02918.x.

Abstract

Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by intervening at one or more stages of carcinogenesis. Recently, resveratrol, a natural product found in the diet of humans, has been shown to function as a cancer chemopreventive agent. Resveratrol was first shown to act as an antioxidant and antimutagenic agent, thus acting as an anti-initiation agent. Further evidence indicated that resveratrol selectively suppresses the transcriptional activation of cytochrome P-450 1A1 and inhibits the formation of carcinogen-induced preneoplastic lesions in a mouse mammary organ culture model. Resveratrol also inhibits the formation of 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted mouse skin tumors in the two-stage model. The enzymatic activities of COX-1 and -2 are inhibited by resveratrol in cell-free models, and COX-2 mRNA and TPA-induced activation of protein kinase C and AP-1-mediated gene expression are suppressed by resveratrol in mammary epithelial cells. In addition, resveratrol strongly inhibits nitric oxide generation and inducible nitric oxide synthase protein expression. NF kappa B is strongly linked to inflammatory and immune responses and is associated with oncogenesis in certain models of cancer, and resveratrol suppresses the induction of this transcription factor by a number of agents. The mechanism may involve decreasing the phosphorylation and degradation of I kappa B alpha. At the cellular level, resveratrol also induces apoptosis, cell cycle delay or a block in the G(1) --> S transition phase in a number of cell lines. Thus, resveratrol holds great promise for future development as a chemopreventive agent that may be useful for several disorders. Preclinical toxicity studies are underway that should be followed by human clinical trials.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology*
  • Humans
  • Neoplasms / prevention & control*
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Stilbenes
  • Resveratrol