Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells

Kotha Subbaramaiah, Pedro Michaluart, Michael B. Sporn, Andrew J. Dannenberg

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

We investigated the effects of ursolic acid, a chemopreventive agent, on the expression of cyclooxygenase-2 (COX-2) in phorbol 12-myristate 13-acetate (PMA)-treated human mammary and oral epithelial cells. Treatment with ursolic acid suppressed PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Ursolic acid also suppressed the induction of COX-2 mRNA by PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by ursolic acid. Transient transfections indicated that the effects of PMA were mediated by a cyclic AMP response element in the COX-2 promoter. Ursolic acid inhibited PMA-mediated activation of protein kinase C, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases. Treatment with PMA increased activator protein-1 activity and the binding of c-Jun to the cyclic AMP response element of the COX-2 promoter, effects that were blocked by ursolic acid. These data are important for understanding the anticancer and anti-inflammatory properties of ursolic acid.

Original languageEnglish (US)
Pages (from-to)2399-2404
Number of pages6
JournalCancer research
Volume60
Issue number9
StatePublished - May 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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