Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. Subbaramaiah, K, Chung, W J, Michaluart, P, Telang, N, Tanabe, T, Inoue, H, Jang, M, Pezzuto, J M, & Dannenberg, A J The Journal of Biological Chemistry, 273(34):21875–21882, August, 1998.
Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells [link]Paper  abstract   bibtex   
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-alpha, 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.
@article{subbaramaiah_resveratrol_1998,
	title = {Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells},
	volume = {273},
	issn = {0021-9258},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9705326},
	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-alpha, 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.},
	number = {34},
	urldate = {2012-01-04},
	journal = {The Journal of Biological Chemistry},
	author = {Subbaramaiah, K and Chung, W J and Michaluart, P and Telang, N and Tanabe, T and Inoue, H and Jang, M and Pezzuto, J M and Dannenberg, A J},
	month = aug,
	year = {1998},
	pmid = {9705326},
	keywords = {Anti-Inflammatory Agents, Non-Steroidal, Breast, Cells, Cultured, Cyclooxygenase 2, Enzyme Induction, Enzyme Inhibitors, Epithelial Cells, Female, Humans, Isoenzymes, Membrane Proteins, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Stilbenes, Tetradecanoylphorbol Acetate, Transcription, Genetic},
	pages = {21875--21882},
}

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