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

92 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

Cyclooxygenase 2
Apoptosis
Breast Neoplasms
MAP Kinase Kinase 2
Stilbenes
Mitogen-Activated Protein Kinase 3
resveratrol
Cyclooxygenase 2 Inhibitors
p53 Genes
Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Small Interfering RNA
Carcinogenesis
Cell Culture Techniques
Phosphorylation
Gene Expression

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. / Tang, Heng Yuan; Shih, Ai; Cao, H. James; Davis, Faith B.; Davis, Paul J.; Lin, Hung Yun.

In: Molecular Cancer Therapeutics, Vol. 5, No. 8, 08.2006, p. 2034-2042.

Research output: Contribution to journalArticle

Tang, Heng Yuan ; Shih, Ai ; Cao, H. James ; Davis, Faith B. ; Davis, Paul J. ; Lin, Hung Yun. / Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. In: Molecular Cancer Therapeutics. 2006 ; Vol. 5, No. 8. pp. 2034-2042.
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