Induction of CYP1A by green tea extract in human intestinal cell lines

In this study the influence of green tea extract (GTE) or its component epigallocatechin gallate (EGCG) on the expression of different cytochrome P450 (CYP) isoenzymes was investigated in the human gastrointestinal epithelial cell lines LS-180 and Caco-2. Additionally, the effect of GTE or EGCG on functional activity of different CYP isoenzymes was investigated in vitro. mRNA expression levels were determined by quantitative RT-PCR and compared with protein levels. In LS-180 cells GTE, but not EGCG, significantly induced CYP1A2 mRNA expression, whereas neither CYP1A1 nor CYP3A4 mRNA expression was modulated by GTE or EGCG. In Caco-2 cells CYP1A1 as well as CYP1A2 mRNA expression was significantly increased in a dose-dependent manner by GTE and EGCG. However, EGCG alone was about 3-5-fold less effective than GTE. mRNA expression of CYP1A1 or CYP1A2 induced by the promutagen benzo[a]pyrene was significantly down-regulated by EGCG but not by GTE. CYP1A protein levels in response to GTE in Caco-2 and LS-180 cells confirmed the mRNA expression results. CYP activity was measured with CYP1A2 or CYP3A4 expressed in insect cell membranes using a luminescent method. GTE or EGCG significantly inhibited CYP1A2 and CYP3A4 function in a dose-dependent manner. Therefore, it appears that green tea moderately modulates the expression of drug-metabolizing enzymes but non-specifically inhibits the function of human CYPs. Since CYP enzymes play an important role in detoxification processes, these results might be of relevance for the prediction of the outcome of future clinical studies.