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Research ArticleArticle

Resveratrol Has Antagonist Activity on the Aryl Hydrocarbon Receptor: Implications for Prevention of Dioxin Toxicity

Robert F. Casper, Monique Quesne, Ian M. Rogers, Takuhiko Shirota, André Jolivet, Edwin Milgrom and Jean-François Savouret
Molecular Pharmacology October 1999, 56 (4) 784-790;
Robert F. Casper
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Monique Quesne
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Ian M. Rogers
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Takuhiko Shirota
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André Jolivet
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Edwin Milgrom
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Jean-François Savouret
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Abstract

Aryl hydrocarbon receptor (AhR) ligands such as dioxin and benzo[a]pyrene are environmental contaminants with many adverse health effects, including immunosuppression, carcinogenesis, and endothelial cell damage. We show here that a wine component, resveratrol (3,5,4′-trihydroxystilbene), is a competitive antagonist of dioxin and other AhR ligands. Resveratrol promotes AhR translocation to the nucleus and binding to DNA at dioxin-responsive elements but subsequent transactivation does not take place. Resveratrol inhibits the transactivation of several dioxin-inducible genes including cytochrome P-450 1A1 and interleukin-1β, both ex vivo and in vivo. Resveratrol has adequate potency and nontoxicity to warrant clinical testing as a prophylactic agent against aryl hydrocarbon-induced pathology.

Footnotes

  • Send reprint requests to: Dr. Jean-François Savouret, Institut National de la Santé et de la Recherche Médicale Unit 135, Hôpital de Bicêtre, 78 rue du Général Leclerc, Le Kremlin-Bicêtre, 94270, France. E-mail:savouret{at}infobiogen.fr

  • ↵1 Current affiliation: Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Toronto, The Toronto Hospital, General Division, Toronto, Ontario, Canada.

  • This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer and the Faculté de Médecine Paris-Sud, and the Medical Research Council of Canada. R. F. C. was supported by a joint Medical Research Council of Canada/Institut National de la Santé et de la Recherche Médicale visiting scientist award.

  • Abbreviations:
    AhR
    aryl hydrocarbon receptor
    PAH
    polycyclic aromatic hydrocarbons
    BaP
    benzo[a]pyrene
    TCDD
    2,3,7,8-tetrachlorodibenzo-p-dioxin
    TC[1,6-3H]DD
    2,3,7,8-tetrachloro[1,6-3H]dibenzo-p-dioxin
    DRE
    dioxin responsive element
    CAT
    chloramphenicol acetyl transferase
    TK
    thymidine kinase promoter
    α-NF
    α-naphthoflavone
    NQOR
    NAD(P)H quinone oxidoreductase
    Il-1β
    interleukin-1β
    GFP
    green fluorescent protein
    DMBA
    7,12-dimethylbenzanthracene
    I3C
    indole-3-carbinol
    LTR
    long terminal repeat
    • Received February 8, 1999.
    • Accepted June 22, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 56 (4)
Molecular Pharmacology
Vol. 56, Issue 4
1 Oct 1999
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Research ArticleArticle

Resveratrol Has Antagonist Activity on the Aryl Hydrocarbon Receptor: Implications for Prevention of Dioxin Toxicity

Robert F. Casper, Monique Quesne, Ian M. Rogers, Takuhiko Shirota, André Jolivet, Edwin Milgrom and Jean-François Savouret
Molecular Pharmacology October 1, 1999, 56 (4) 784-790;

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Research ArticleArticle

Resveratrol Has Antagonist Activity on the Aryl Hydrocarbon Receptor: Implications for Prevention of Dioxin Toxicity

Robert F. Casper, Monique Quesne, Ian M. Rogers, Takuhiko Shirota, André Jolivet, Edwin Milgrom and Jean-François Savouret
Molecular Pharmacology October 1, 1999, 56 (4) 784-790;
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