Resveratrol and apoptosis

Hung Yun Lin, Heng Yuan Tang, Faith B. Davis, Paul J. Davis

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Resveratrol is a naturally occurring stilbene with desirable cardioprotective and anti-cancer properties. We have demonstrated the existence of a plasma membrane receptor for resveratrol near the arginine-glycine-aspartate (RGD) recognition site on integrin α vβ 3 that is involved in stilbene-induced apoptosis of cancer cells. Resveratrol treatment in vitro causes activation and nuclear translocation of mitogen-activated protein kinase (ERK1/2), consequent phosphorylation of Ser-15 of p53, and apoptosis. An RGD peptide blocks these actions of resveratrol. By a PD98059-inhibitable process, resveratrol causes inducible COX-2 to accumulate in the nucleus where it complexes with pERK1/2 and p53. Chromatin immunoprecipitation reveals binding of nuclear COX-2 to promoters of certain p53-responsive genes, including PIG3 and Bax. NS-398, a specific pharmacologic inhibitor of COX-2, prevents resveratrol-induced complexing of nuclear ERK1/2 with COX-2 and with pSer-15-p53 and subsequent apoptosis; cyclooxygenase enzyme activity is not involved. Molecular steps in the pro-apoptotic action of resveratrol in cancer cells include induction of intranuclear COX-2 accumulation relevant to activation of p53. Epidermal growth factor, estrogen, and thyroid hormone act downstream of ERK1/2 to prevent resveratrol-induced apoptosis.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1215
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Keywords

  • Apoptosis
  • COX-2
  • ERK1/2
  • Integrin α β
  • P53
  • Resveratrol

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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