Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.
A large body of evidence suggests that inhibiting cyclooxygenase-2 (COX-2), the inducible form of COX, will be an important strategy for preventing cancer. In this study, we investigated whether resveratrol, a chemopreventive agent found in grapes, could suppress phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induced COX-2 mRNA, COX-2 protein, and prostaglandin synthesis. These effects were inhibited by resveratrol. Nuclear runoffs 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 and the induction of COX-2 promoter activity by c-Jun. Phorbol ester-mediated induction of AP-1 activity was blocked by resveratrol. These data are likely to be important for understanding the anticancer and anti-inflammatory properties of resveratrol.
Subbaramaiah
K
K
Department of Medicine, New York Presbyterian Hospital-Cornell, New York 10021, USA. ksubba@mail.med.cornell.edu
Michaluart
P
P
Chung
W J
WJ
Tanabe
T
T
Telang
N
N
Dannenberg
A J
AJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000201:enzymology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013267:Stilbenes; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077185:Resveratrol