Epigenetic modulation of the retinoid X receptor α by green tea in the azoxymethane-ApcMin/+ mouse model of intestinal cancer

✍ Scribed by Suresh R. Volate; Stephanie J. Muga; Ala Y. Issa; Daniela Nitcheva; Theresa Smith; Michael J. Wargovich

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 690 KB
• Volume: 48
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20542

✦ Synopsis

Abstract

We investigated the possible mechanisms of inhibition of colorectal carcinogenesis by green tea (GT) in azoxymethane‐treated (AOM) Apc^Min/+^ mice. Mice received water or a 0.6% (w/v) solution of GT as the only source of beverage. GT treatment commenced at the 8th week of age and lasted for 8 wk. The treatment caused a statistically significant reduction in the number of newly formed tumors (28%, P < 0.05). Immunohistochemical analysis showed that GT decreased the levels of β‐catenin and its downstream target cyclin D1. To probe a mechanism, we further investigated the expression of retinoic X receptor alpha (RXRα) in AOM/Apc^Min/+^ tumors. Our results show that RXRα is selectively downregulated in AOM/Apc^Min/+^ mouse intestinal tumors. In contrast, other retinoic receptors including retinoic acid receptor alpha (RARα), RARβ, RXRβ, and RXRγ were all expressed in Apc^Min/+^ adenomas. Furthermore, our results show that RXRα downregulation is an early event in colorectal carcinogenesis and is independent of β‐catenin expression. GT significantly increased the protein levels of RXRα. In addition, RT‐PCR analysis showed that GT induced a similar increase in the levels of RXRα mRNA. Genomic bisulfite treatment of colonic DNA followed by pyrosequencing of 24 CpG sites in the promoter region of RXRα gene showed a significant decrease in CpG methylation with GT treatment. The results suggest that a low concentration of GT is sufficient to desilence RXRα and inhibit intestinal tumorigenesis in the Apc^Min/+^ mouse. Mol. Carcinog. © 2009 Wiley‐Liss, Inc.