Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells Journal Article
| Authors: | Subbaramaiah, K.; Chung, W. J.; Michaluart, P.; Telang, N.; Tanabe, T.; Inoue, H.; Jang, M.; Pezzuto, J. M.; Dannenberg, A. J. |
| Article Title: | Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells |
| Abstract: | We determined whether resveratrol, a phenolic antioxidant found in grapes and other food products, inhibited phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induces COX-2 and causes a marked increase in the production of prostaglandin E2. These effects were inhibited by resveratrol. Resveratrol suppressed PMA-mediated increases in COX-2 mRNA and protein. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. PMA caused about a 6-fold increase in COX-2 promoter activity, which was suppressed by resveratrol. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, indicated that the effects of PMA and resveratrol were mediated via a cyclic AMP response element. Resveratrol inhibited PMA- mediated activation of protein kinase C. Overexpressing protein kinase C-α, ERK1, and c-Jun led to 4.7-, 5.1-, and 4-fold increases in COX-2 promoter activity, respectively. These effects also were inhibited by resveratrol. Resveratrol blocked PMA-dependent activation of AP-1-mediated gene expression. In addition to the above effects on gene expression, we found that resveratrol also directly inhibited the activity of COX-2. These data are likely to be important for understanding the anti-cancer and anti- inflammatory properties of resveratrol. |
| Keywords: | human cell; promoter region; cells, cultured; enzyme inhibition; breast; transcription initiation; membrane proteins; transcription, genetic; carcinogenesis; enzyme inhibitors; eukaryota; cyclooxygenase 2; anti-inflammatory agents, non-steroidal; immunoblotting; epithelium cell; epithelial cells; gene control; protein kinase c; antiinflammatory activity; antioxidant activity; resveratrol; mutagenesis; breast cell; isoenzymes; phorbol ester; enzyme induction; northern blotting; tetradecanoylphorbol acetate; enhancer region; promoter regions (genetics); prostaglandin-endoperoxide synthases; stilbenes; humans; human; female; priority journal; article; vitaceae |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 273 |
| Issue: | 34 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1998-08-21 |
| Start Page: | 21875 |
| End Page: | 21882 |
| Language: | English |
| DOI: | 10.1074/jbc.273.34.21875 |
| PUBMED: | 9705326 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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