The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone

Hung Y. Lin, Paul J. Davis, Heng Yuan Tang, Shaker A. Mousa, Mary K. Luidens, Aleck H. Hercbergs, Faith B. Davis

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Constitutively expressed cyclooxygenase-2 (COX-2) is a marker of tumor cell aggressiveness. Inducible COX-2 has also been described in cancer cells and localizes in the cancer cell nucleus, where formation of a complex of mitogen-activated protein kinase (MAPK) and COX-2 is antecedent to p53-dependent apoptosis. The stilbene resveratrol is a model pharmacologic activator of this pro-apoptotic mechanism. Physiological concentrations of thyroid hormone are anti-apoptotic in several types of tumor cells. A mechanism by which the hormone is antiapoptotic is disruption of the nuclear MAPK-COX-2 complex. We review here the apoptosis-relevant effects of resveratrol and thyroid hormone and then speculate about the significance of convergence of these actions in cancer cells in the intact organism. Clinical activity of resveratrol may be modulated by normal tissue levels of endogenous thyroid hormone, and hypothyroidism in the cancer patient - whether spontaneous or induced by chemotherapeutic agents - may permit full expression of the apoptotic activity of the administered stilbene. Chronic pharmacologic inhibition of COX-2 may oppose the pro-apoptotic effect of resveratrol.

Original languageEnglish
Pages (from-to)1877-1882
Number of pages6
JournalCell Cycle
Volume8
Issue number12
Publication statusPublished - Jun 15 2009
Externally publishedYes

Keywords

  • Angiogenesis
  • Cyclooxygenase-2
  • Mitogen-activated protein kinase
  • Resveratrol

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

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    Lin, H. Y., Davis, P. J., Tang, H. Y., Mousa, S. A., Luidens, M. K., Hercbergs, A. H., & Davis, F. B. (2009). The pro-apoptotic action of stilbene-induced COX-2 in cancer cells: Convergence with the anti-apoptotic effect of thyroid hormone. Cell Cycle, 8(12), 1877-1882.