Journal Article

Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53

Seung Joon Baek, Leigh C. Wilson and Thomas E. Eling

in Carcinogenesis

Volume 23, issue 3, pages 425-432
Published in print March 2002 | ISSN: 0143-3334
Published online March 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.3.425
Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53

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Dietary phenolic substances including resveratrol, a stillbene compound, are found in several fruits and vegetables, and these compounds have been reported to have anti-oxidant, anti-inflammatory and antitumorigenic activities. However, the molecular mechanisms underlying the antitumorigenic or chemopreventive activities of these compounds remain largely unknown. The expression of NAG-1 [non-steroidal anti-inflammatory (NSAID) drug-activated gene-1], a member of the transforming growth factor-beta (TGF-β) superfamily, has been shown to be associated with pro-apoptotic and antitumorigenic activities. Here, we have demonstrated that resveratrol induces NAG-1 expression and apoptosis in a concentration-dependent manner. Resveratrol increases the expression of p53, tumor suppressor protein, prior to NAG-1 induction, indicating that NAG-1 expression by resveratrol is mediated by p53 expression. We also show that the p53 binding sites within the promoter region of NAG-1 play a pivotal role to control NAG-1 expression by resveratrol. Derivatives of resveratrol were examined for NAG-1 induction, and the data suggest that resveratrol-induced NAG-1 and p53 induction is not dependent on its anti-oxidant activity. The data may provide linkage between p53, NAG-1 and resveratrol, and in part, a new clue to the molecular mechanism of the antitumorigenic activity of natural polyphenolic compounds.

Keywords: COX, cyclooxygenase;; FACS, fluorescence-activated cell sorter;; MTS/PMS, Owen's reagent-phenazine methosulphate;; NAG-1, NSAID-activated gene-1;; NSAIDs, non-steroidal anti-inflammatory drugs;; PCR, polymerase chain reaction;; RIPA, radioimmunoprecipitation;; TGF-β, transforming growth factor-beta;; TPA, 12-O-tetradecanoylphorbol acetate.

Journal Article.  6320 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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