Protective effects of epigallocatechin gallate on colon preneoplastic lesions induced by 2-amino-3-methylimidazo[4,5-f ] quinoline in mice.
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.
Yuan
Jun-Hua
JH
Department of Digestive Disease, Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, People's Republic of China.
Li
Yan-Qing
YQ
Yang
Xiao-Yun
XY
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens / Q000008:administration & dosage*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D011804:Quinolines / Q000008:administration & dosage*; D015398:Signal Transduction; D013662:Tea / Q000737:chemistry; D016896:Treatment Outcome
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D051267:NF-E2-Related Factor 2; D011804:Quinolines; D013662:Tea; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D002392:Catechin; C045651:epigallocatechin gallate; C476725:bilirubin uridine-diphosphoglucuronosyl transferase 1A10; D014453:Glucuronosyltransferase