Effects of ready to drink teas on AhR- and PXR-mediated expression of cytochromes P450 CYP1A1 and CYP3A4 in human cancer cell lines and primary human hepatocytes

摘要

A variety of xenobiotics are taken in the diet and they can interfere with regulatory pathways of drug metabolizing enzymes in humans. This can result in food-drug interactions, which is undesirable clinical situation where drug pharmacokinetics are influenced by dietary compounds. Xenobiotics-mediated food-drug interactions include the induction of drug metabolizing cytochromes P450. The expression of the most important inducible cytochromes CYP1A and CYP3A4 are regulated by xenoreceptors PXR and AhR. We examined extracts from 17 different flavoured ready to drink teas (RDTs) for their capabilities to activate PXR and AhR receptors and to induce CYP3A4 and CYP1A genes. Primary cultures of human hepatocytes and cancer cell lines HepG2 and LS174T were used as in vitro models. Gene reporter assays, RT-PCR and Western blots were performed. We identified three RDTs that induced CYP3A4 mRNA and protein, implying a potential for food-drug interactions. Several RDTs slightly elevated CYP1A1 expression or activated AhR.