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

Susanne N. Williams, Hsueh Shih, Denis K. Guenette, William Brackney, Michael S. Denison, George V. Pickwell, Linda C. Quattrochi

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Green tea possesses significant anticancer activity in numerous experimental animal models, including demonstrated protection against aryl hydrocarbon induced cancers. The aryl hydrocarbon receptor (AhR) mediates the transcriptional activation of CYP1A1 and CYP1A2. In the present study, we investigated the effects of commercially available green tea extracts (GTEs) and individual tea catechins on the function of the AhR and on CYP1A gene expression in human hepatoma HepG2 cells and primary cultures of human hepatocytes. GTEs inhibited the transcription of a human CYP1A1 promoter-driven reporter 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 determine if the observed effects were due to a single green tea component, we examined the four major catechins present in GTEs. Only (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea, was able to inhibit TCDD-induced binding of the AhR to DNA and subsequent CYP1A transcription, however EGCG alone was less effective than GTEs. We next examined GTEs and catechins for AhR agonist activity. GTEs caused a concentration-dependent increase in CYP1A1-promoter driven reporter gene activity and caused accumulation of CYP1A1 mRNA and protein, but we found that individual catechins were unable to induce the expression of CYP1A1. Our results demonstrate that GTEs as a whole exert mixed agonist/antagonist activity on the AhR, while EGCG functions as a strict AhR antagonist. Therefore, modulation of human CYP1A expression by green tea extracts can not be attributed to the action of a single tea catechin, but rather is due to the effects of a complex mixture. These findings may be useful in future studies concerning green tea as a cancer preventive agent. (C) 2000 Published by Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)211-229
Number of pages19
JournalChemico-Biological Interactions
Volume128
Issue number3
DOIs
StatePublished - Nov 1 2000

Keywords

  • Aryl hydrocarbon receptor
  • CYP1A
  • Flavonoids
  • Green tea
  • HepG2
  • Human hepatocytes

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression'. Together they form a unique fingerprint.

Cite this