Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells Academic Article Article uri icon

Overview

MeSH Major

  • Adiponectin
  • Adipose Tissue, White
  • Aromatase
  • Breast
  • C-Reactive Protein
  • Interleukin-6
  • Leptin
  • Menopause

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.

publication date

  • August 21, 1998

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1074/jbc.273.34.21875

PubMed ID

  • 9705326

Additional Document Info

start page

  • 21875

end page

  • 82

volume

  • 273

number

  • 34