Resveratrol inhibits the expression of cyclooxygenase-2 in human mammary and oral epithelial cells

We determined whether resveratrol, a phenolic anti-oxidant found in grapes and wine, inhibited phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induced COX-2 mRNA and protein and caused a marked increase in PGE₂ synthesis. These effects were inhibited by resveratrol. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. Resveratrol inhibited PMA-mediated activation of protein kinase C (PKC) and the induction of COX-2 promoter activity by c-Jun. Phorbol ester-mediated induction of AP-1 activity was blocked by resveratrol. In addition to the above effects on COX-2 gene expression, resveratrol also directly inhibited COX-2 enzyme activity. These data are likely to be important for understanding the anti-inflammatory and anti-cancer properties of resveratrol.