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Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells
K Subbaramaiah1, P Michaluart, W J Chung
1Department of Medicine, New York Presbyterian Hospital-Cornell, New York 10021, USA. ksubba@mail.med.cornell.edu
Abstract:
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.
Insights
Resveratrol, a compound found in grapes, inhibits the induction of cyclooxygenase-2 (COX-2) in human cells. This finding is important for understanding the anticancer and anti-inflammatory properties of resveratrol.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) is a key enzyme implicated in cancer development.
- Inhibiting COX-2 is a potential strategy for cancer chemoprevention.
- Resveratrol, a natural polyphenol from grapes, exhibits chemopreventive properties.
Purpose of the Study:
- To investigate the effect of resveratrol on phorbol ester (PMA)-induced COX-2 expression in human mammary and oral epithelial cells.
- To elucidate the molecular mechanisms by which resveratrol suppresses COX-2 induction.
Main Methods:
- Cell culture of human mammary and oral epithelial cells.
- Treatment with phorbol ester (PMA) and resveratrol.
- Analysis of COX-2 mRNA and protein levels.
- Measurement of prostaglandin synthesis.
- Nuclear runoff assays to assess transcription rates.
- Assays for protein kinase C activation, COX-2 promoter activity, and AP-1 activity.
Main Results:
- PMA treatment increased COX-2 mRNA, protein, and prostaglandin synthesis.
- Resveratrol inhibited PMA-induced COX-2 expression and prostaglandin synthesis.
- Resveratrol suppressed PMA-mediated increases in COX-2 transcription rates.
- Resveratrol blocked PMA-induced activation of protein kinase C, c-Jun-mediated COX-2 promoter activity, and AP-1 activity.
Conclusions:
- Resveratrol effectively suppresses PMA-induced COX-2 in human epithelial cells.
- Resveratrol acts, in part, by inhibiting protein kinase C and AP-1 signaling pathways.
- These findings support the potential of resveratrol as an anticancer and anti-inflammatory agent.