Resveratrol decreases basal and induced CYP1AI mRNA/protein levels in both
in vitro and in vivo models, and some studies suggest that resveratrol acts
as an aryl hydrocarbon receptor (AhR) antagonist. Treatment of T47D or MCF
-7 cells with 10 muM resveratrol inhibited induction of CYP1AI mRNA and CYP
1AI-dependent activity after treatment with 2,3,7,8-tetrachlorodibenzo-p-di
oxin (TCDD), as previously reported. In contrast, resveratrol did not inhib
it TCDD-induced reporter gene activity in cells transfected with an Ah-resp
onsive construct containing a human CYP1AI gene promoter insert, whereas 3'
-methoxy-4'-nitroflavone, a "pure" AhR antagonist, inhibited this response.
Resveratrol induced transformation of the rat cytosolic AhR and, after tre
atment of T47D and MCF-7 cells with resveratrol, a transformed nuclear AhR
complex was observed. In contrast to 3'-methoxy-4'-nitroflavone, resveratro
l did not block TCDD-induced AhR transformation in vitro or nuclear uptake
of the AhR complex in breast cancer cells. Thus, the action of resveratrol
on the AhR was consistent with that of an AhR agonist; however, resveratrol
did not exhibit functional AhR agonist or antagonist activities in breast
cancer cells. Actinomycin D chase experiments in T47D cells showed that res
veratrol. and dehydroepiandrosterone both increased the rate of CYP1AI mRNA
degradation, whereas resveratrol did not affect CYP1AI-dependent activity
in cells pretreated with TCDD for 18 hr. These data suggest that resveratro
l inhibits CYP1AI via an AhR-independent post-transcriptional pathway. (C)
2001 Elsevier Science Inc. All rights reserved.