Effects of green tea extract and epigallocatechin-3-gallate (EGCG) on xenobiotic transporter and metabolizing enzyme gene expression profiles in CACO-2 cells

Shu Zhang, Purdue University

Abstract

Green tea extract (GTE) contains a variety of bioactive catechins that are under evaluation as potential anti-inflammatory/antioxidant compounds. The effects of GTE and its major catechin, (-)epigallocatechin gallate (EGCG) on xenobiotic transporter and metabolizing enzyme expression are largely unknown. This study was conducted to examine global gene expression profiles including transporter and metabolizing enzyme expression elicited by GTE and EGCG in cultured human intestinal cells (Caco-2 cells). Caco-2 cells were treated with GTE (100μM of EGCG component), EGCG (100μM) or control media for 72 h (n=4/group). RNA was extracted from the samples, and the expression of >20,000 genes was assessed using the Affymetrix HGU133 Plus 2.0 array. An analysis of variance model (ANOVA) was employed to identify statistically significantly differentially expressed genes. The type I error was controlled at 5% using both Holm's sequential Bonferroni procedure and the False Discovery Rate (FDR). Alterations in expression of cytochrome P450 enzymes (CYPs) and solute carrier transporters were evaluated. Over 20,000 genes were expressed in Caco-2 cells, including >45 transporters/CYPs. Treatment with GTE and EGCG resulted in 2-5 fold induction/inhibition in the expression of at least 326 and 618 genes, respectively. Statistically significant changes in transporter/enzyme expression found by the FDR approach and Holm's sequential Bonferroni procedure were detected for 8 transporters/metabolic enzymes. Green tea catechins broadly affect gene expression in Caco-2 cells, including that of several xenobiotic transporters and metabolic enzymes.^

Degree

M.S.

Advisors

David R. Foster, Purdue University, Kevin M. Sowinski, Purdue University.

Subject Area

Health Sciences, Pharmacology

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