Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression

Green tea possesses significant anticancer activity in numerous experimenta l animal models, including demonstrated protection against aryl hydrocarbon induced cancers. The aryl hydrocarbon receptor (AhR) mediates the transcri ptional activation of CYP1A1 and CYP1A2. In the present study, we investiga ted the effects of commercially available green tea extracts (GTEs) and ind ividual tea catechins on the function of the AhR and on CYP1A gene expressi on in human hepatoma HepG2 cells and primary cultures of human hepatocytes. GTEs inhibited the transcription of a human CYP1A1 promoter-driven reporte r gene induced by the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a concentration-dependent manner and inhibited the induced accumulation of both CYP1A1 and CYP1A2 mRNAs. GTEs blocked TCDD-induced binding of the AhR to DNA in HepG2 cells and in vitro in isolated hepatic cytosol. To dete rmine if the observed effects were due to a single green tea component, we examined the four major catechins present in GTEs. Only (-)-epigallocatechi n gallate (EGCG), the most abundant catechin in green tea, was able to inhi bit TCDD-induced binding of the AhR to DNA and subsequent CYP1A transcripti on, however EGCG alone was less effective than GTEs. We next examined GTEs and catechins for AhR agonist activity. GTEs caused a concentration-depende nt increase in CYP1A1-prometer driven reporter gene activity and caused acc umulation of CYP1A1 mRNA and protein, but we found that individual catechin s were unable to induce the expression of CYP1A1. Our results demonstrate t hat GTEs as a whole exert mixed agonist/antagonist activity on the AhR, whi le EGCG functions as a strict AhR antagonist. Therefore, modulation of huma n CYP1A expression by green tea extracts can not be attributed to the actio n of a single tea catechin, but rather is due to the effects of a complex m ixture. These findings may be useful in future studies concerning green tea as a cancer preventive agent. (C) 2000 Published by Elsevier Science Irela nd Ltd.