| 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. |
| Keywords: |
signal transduction; mitogen activated protein kinase; controlled study; protein expression; human cell; promoter region; carcinoma, squamous cell; breast; cell line; protein binding; membrane proteins; transcription, genetic; antineoplastic activity; drug structure; enzyme activation; drug effect; dose-response relationship, drug; tumor cells, cultured; transfection; transcription regulation; genetic transfection; cyclooxygenase 2; prostaglandin e2; western blotting; breast epithelium; epithelial cells; plasmids; protein kinase c; mitogen-activated protein kinases; tongue neoplasms; blotting, northern; mitogen-activated protein kinase kinases; isoenzymes; phorbol 13 acetate 12 myristate; tetradecanoylphorbol acetate; jnk mitogen-activated protein kinases; prostaglandin synthesis; dinoprostone; map kinase kinase 4; rna, ribosomal, 18s; triterpenes; p38 mitogen-activated protein kinases; protein c jun; prostaglandin-endoperoxide synthases; humans; human; female; priority journal; article; cyclic amp responsive element; ursolic acid
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