Abstract 1866: (−)-Epigallocatechin gallate suppresses azoxymethane-induced colonic preneoplastic lesions in rats by inhibiting the expression and activation of indoleamine 2,3-dioxygenase

Abstract

Abstract Immune escape is involved in the development and progression of several types of tumors. Indoleamine 2,3-dioxygenase (IDO) plays a critical role in the induction of immune tolerance. (−)-Epigallocatechin gallate (EGCG), the major biologically active component of green tea, exerts cancer chemopreventive and anti-carcinogenic effects in various organs. In the present study, we examined the effects of EGCG and 1-methyl-tryptophan (1-MT), an IDO inhibitor, on the development of azoxymethane (AOM)-induced colonic preneoplastic lesions in F344 rats by focusing on the inhibition of IDO activation. To induce colonic premalignant lesions, male F344 rats were given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received drinking water containing 0.1% EGCG or 0.2% 1-MT for 4 weeks, starting 1 week before the first dose of AOM. At sacrifice, drinking water with EGCG and 1-MT significantly decreased the total number of aberrant crypt foci and β-catenin accumulated crypts, which overexpresses IDO protein, compared with the control untreated-rats. Drinking EGCG decreased the expression levels of IDO mRNA on the colonic mucosa of experimental rats. In addition, the enzyme activity of IDO, which was estimated by measuring the serum concentration of kynurenine and tryptophan, was also significantly inhibited by treatment with EGCG and 1-MT. These findings suggest that the up-regulation of IDO is associated with colon carcinogenesis and EGCG prevents this carcinogenesis by inhibiting the expression and activation of IDO. Targeting IDO by using EGCG or IDO inhibitor might be, therefore, a promising strategy for the prevention of colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1866. doi:10.1158/1538-7445.AM2011-1866