Abstract
Resveratrol, a compound present in a variety of plants, was recently shown to have potent chemopreventive activity against aryl hydrocarbon-induced tumorigenesis in mice. Therefore, in the present study, we examined the effect of resveratrol on the function of the aryl hydrocarbon receptor (AHR) and the transcription of CYP1A1 in human HepG2 hepatoma cells. Resveratrol inhibited the increase in cytochrome P450 (CYP) 1A1 mRNA caused by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a concentration-dependent manner. The induction of transcription of an aryl hydrocarbon-responsive reporter vector containing the CYP1A1 promoter by TCDD was likewise inhibited by resveratrol. Resveratrol also inhibited the constitutive level of CYP1A1 mRNA and reporter vector transcription in HepG2 cells. The increase in CYP1A1 enzyme activity induced by TCDD was inhibited by resveratrol. Resveratrol prevented the TCDD-induced transformation of the cytosolic AHR to its nuclear DNA-binding form. However, resveratrol had no effect on the binding of TCDD to the cytosolic AHR. These data demonstrate that resveratrol inhibits CYP1A1 expression in vitro, and that it does this by preventing the binding of the AHR to promoter sequences that regulate CYP1A1 transcription. This activity may be an important part of the chemopreventive activity of resveratrol.
Footnotes
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↵1 Supported in part by federal funds from the National Cancer Institute, NIH, under Contract No. NO1-CO-56000.
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↵2 To whom requests for reprints should be addressed, at Basic Research Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Building 560/Room 12-05, P. O. Box B, Frederick, MD 21702-1201. Phone: (301) 846-5160; Fax: (301) 846-6093; E-mail: hciolino@mail.ncifcrf.gov.
- Received July 8, 1998.
- Accepted October 15, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 24
