Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells

Heng Yuan Tang, Ai Shih, H. James Cao, Faith B. Davis, Paul J. Davis, Hung Yun Lin

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Cyclooxygenase-2 (COX-2) is antiapoptotic and is implicated in tumorigenesis. Recent reports, however, have also ascribed a proapoptotic action to inducible COX-2. We show here for the first time that a stilbene, resveratrol, induces nuclear accumulation of COX-2 protein in human breast cancer MCF-7 and MDA-MB-231 cell cultures. The induction of COX-2 accumulation by resveratrol is mitogen-activated protein kinase (MAPK; extracellular signal -regulated kinase 1/2)- and activator protein 1-dependent. Nuclear COX-2 in resveratrol-treated cells colocalizes with Ser 15-phosphorylated p53 and with p300, a coactivator for p53-dependent gene expression. The interaction of COX-2, p53, and p300, as well as resveratrol-induced apoptosis, was inhibited by a MAPK activation inhibitor, PD98059. A specific inhibitor of COX-2, NS398, and small interfering RNA knockdown of COX-2 were associated with reduced p53 phosphorylation and consequent decrease in p53-dependent apoptosis in resveratrol-treated cells. We conclude that nuclear accumulation of COX-2 can be induced by resveratrol and that the COX has a novel intranuclear colocalization with Ser 15-phosphorylated p53 and p300, which facilitates apoptosis in resveratrol-treated breast cancer cell.

Original languageEnglish
Pages (from-to)2034-2042
Number of pages9
JournalMolecular Cancer Therapeutics
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this