Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells

Authors
Citation
Je. Lee et S. Safe, Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells, BIOCH PHARM, 62(8), 2001, pp. 1113-1124
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1113 - 1124
Database
ISI
SICI code
0006-2952(20011015)62:8<1113:IOAPMI>2.0.ZU;2-Z
Abstract
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.