Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.
J Biol Chem
; 273(34): 21875-82, 1998 Aug 21.
Article
em En
| MEDLINE
| ID: mdl-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
/
Transcrição Gênica
/
Mama
/
Anti-Inflamatórios não Esteroides
/
Prostaglandina-Endoperóxido Sintases
/
Inibidores Enzimáticos
/
Isoenzimas
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos