> [The drug salicylamide is an antagonist of the aryl hydrocarbon
Effect of cur***in on the aryl hydrocarbon receptor and cytochrome
P450 1A1 in MCF-7 human breast carcinoma cells.
We examined the interaction of cur***in, a dietary constituent and
chemopreventive compound, with the carcinogen activation pathway
mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 mammary
epithelial carcinoma cells. Cur***in caused a rapid ac***ulation of
cytochrome P450 1A1 (CYP1A1) mRNA in a time- and concentration-
dependent manner, and CYP1A1 monooxygenase activity increased as
measured by ethoxyresorufin-O-deethylation. Cur***in activated the DNA-
binding capacity of the AhR for the xenobiotic responsive element of
CYP1A1 as measured by the electrophoretic-mobility ****ft assay (EMSA).
Cur***in was able to compete with the prototypical AhR ligand 2,3,7,8-
tetrachlorodibenzo-p-dioxin for binding to the AhR in isolated MCF-7
cytosol, indicating that it interacts directly with the receptor.
Although cur***in could activate the AhR on its own, it partially
inhibited the activation of AhR, as measured by EMSA, and partially
decreased the ac***ulation of CYP1A1 mRNA caused by the mammary
carcinogen dimethylbenzanthracene (DMBA). Cur***in competitively
inhibited CYP1A1 activity in DMBA-treated cells and in microsomes
isolated from DMBA-treated cells. Cur***in also inhibited the
metabolic activation of DMBA, as measured by the formation of DMBA-DNA
adducts, and decreased DMBA-induced cytotoxicity. These results
suggest that the chemopreventive effect of cur***in may be due, in
part, to its ability to compete with aryl hydrocarbons for both the
AhR and CYP1A1. Cur***in may thus be a natural ligand and substrate of
the AhR pathway. PMID: 9698073
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