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.
Highlights
Colorectal cancer is a significant cause of mortality in Western countries and is the second most common type of fatal cancer [1]
Our previous studies showed that sulforaphane [26] and Epigallocatechin gallate (EGCG) [27] could induce the expression of UGT1A family members in vitro. We demonstrated that this upregulation was due to the actions of transcription factor NF-E2–related factor 2 (Nrf2)
We propose one mechanism where the protective effects of EGCG on IQ-induced colonic aberrant crypt foci would involve induction of isoform UGT1A10 in mice gastrointestinal tract via Nrf2 signal pathway
Summary
Colorectal cancer is a significant cause of mortality in Western countries and is the second most common type of fatal cancer [1]. The risk factors for developing colorectal cancer include hereditary considerations as well as environmental factors, which can include genotoxins and cocarcinogens ingested in alimentation [2]. Some of these genotoxic chemicals are formed during food preparation, such as heterocyclic aromatic amines (HAA) produced during the cooking of food with high creatine, free amino acid, and sugar content [3,4,5]. Among all the components of HAA, 2-amino-3methylimidazo[4,5-f ]quinoline (IQ) is commonly found in the human diet [6,7,8,9].
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