Protective Effects of Epigallocatechin Gallate on Colon Preneoplastic Lesions Induced by 2-Amino-3-Methylimidazo(4,5-f)Quinoline in Mice

Abstract

Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has multiple anticarcinogenic effects. The aim of the present study was to investigate if EGCG could prevent the formation of colon aberrant crypt foci (ACF) induced by 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) and to explore possible mechanisms for resultant effects. Sixty male BALB/cA nude, immunodeficient mice were divided into six groups including a normal unexposed control, mice induced with IQ alone, three groups treated with varying doses of EGCG post-IQ induction, and a EGCG-treated control population. Six weeks later, the mice were killed, and tissues subjected to hematoxylin-eosin (H&E) and 0.2% methylene blue staining to observe histopathological alterations of colon mucus and the formation of ACF, respectively. Protein expression of NF-E2-related factor 2 (Nrf2) was assessed via immunohistochemistry (IHC) and Western analysis, and mRNA levels of Nrf2 and uridine 5′-diphosphate-glucuronosyltransferase (UGT)1A10 were determined in colon tissues. Our results demonstrate that, compared with IQ-induced controls, the degree of atypical hyperplasia decreased and the number of total ACF and total AC also decreased significantly (P < 0.05 and P < 0.01, respectively) in mice belonging to all EGCG dosing groups. At the same time, the protein levels of Nrf2 detected by IHC and Western blotting increased (both P < 0.01 compared with IQ group), and the mRNA levels of Nrf2 and UGT1A10 increased (both P < 0.01 compared with IQ group). In conclusion, EGCG had preventive effects on preneoplastic lesions induced by IQ. Our observations suggest that this effect may be the result of activation of the Nrf2-UGT1A10 signaling pathway.

Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice

“…It is possible that the induction of these antioxidant defenses occurs downstream from the transcriptional activation of NF-E2-related factor-2 (Nrf2) via its interaction with the antioxidant-response element (ARE) [38]. Indeed, EGCG has been shown to increase Nrf2 nuclear translocation and ARE transcriptional activity in vitro [36] and up-regulate Nrf2 protein expression in a mouse model [39]. These GTE-mediated antioxidant activities are important because membrane peroxidation induces cellular damage and activates NFκB-mediated responses that induce proinflammatory cytokine expression including TNF-α [3], which contribute to NAFLD [40].…”

Protective effects of epigallocatechin gallate (EGCG) derivatives on azoxymethane-induced colonic carcinogenesis in mice

“…(nuclear factor E2-related factor 2-uridine 5 0 -diphosphate glucuronosyltransferase, a phase II metabolism) signalling pathway, among others Yuan et al, 2008). Esterification of EGCG with fatty acids employed in this study might have led to improved lipophilicity and membrane affinity (data shown in , 2012, and presumably enhanced absorption through the intestine.…”

“…Both hereditary and environmental factors (through ingestion of genotoxins and carcinogens in alimentation) contribute to the development of CRC (Yuan, Li, & Yang, 2008). The pathogenesis of CRC involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries (Raju, 2008).…”

Molecular basis of chemoprevention with dietary phytochemicals: redox-regulated transcription factors as relevant targets

“…Intraperitoneal administration of EGCG, at a dose equivalent to four cups of 2% tea for 15 days, elevated the levels of GST, GPx, SOD and catalase in mouse liver, and reduced lipid peroxidation and cell proliferation during the dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted mouse skin carcinogenesis (Saha and Das 2002). EGCG, given by gavage, significantly decreased 2-amino-3-methylimidazo[4,5-f]quinoline-induced atypical hyperplasia, the number of aberrant crypt foci and adenocarcinoma formation by activating Nrf2 and upregulating UGT1A10 in mouse colon (Yuan et al 2008). The compound also enhanced the mRNA expression of GCL and GSTp, and the nuclear translocation and the ARE binding of Nrf2 in human mammary epithelial cells .…”