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Carcinogenesis Advance Access published online on September 24, 2007
Carcinogenesis, doi:10.1093/carcin/bgm204
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethane-treated F344 rats

Hang Xiao*, Xingpei Hao*, Barbara Simi, Jihyeung Ju, Heyuan Jiang, Bandaru S. Reddy and Chung S. Yang{dagger}

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020

{dagger} Corresponding Author: Chung S. Yang, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA, Tel: (732) 445-3400 x 244; Fax: (732) 445-0687, Email: csyang{at}rci.rutgers.edu

Green tea and its constituents have shown cancer preventive activities in many animal models. In order to prepare for a human trial on the inhibition of colon carcinogenesis, we conducted a study with green tea polyphenols as the preventive agent in an azoxymethane (AOM)-induced rat colon cancer model using aberrant crypt foci (ACF) as an endpoint. F344 rats were given two weekly injections of AOM (15 mg/kg), and then fed a 20% high fat diet with or without 0.12% or 0.24% Polyphenon E (PPE, a standardized green tea preparation consisting of 65% of EGCG and 22% other catechins) for 8 weeks. Colorectal ACF were analyzed under a microscope after methylene blue staining. Dietary PPE administration was found to significantly and dose-dependently decrease the total number of ACF per rat and the total number of aberrant crypt per rat. Moreover, treatment with 0.24% PPE also significantly decreased the percentage of large ACF (4 or more crypts) and the percentage of ACF with high-grade dysplasia in total ACF. The high-grade dysplastic ACF from 0.24% PPE-treated group had increased apoptosis and decreased nuclear expression levels of ß-catenin and cyclin D1. Retinoid X receptor {alpha} (RXR{alpha}) expression was reduced in high-grade dysplastic ACF, adenoma, and adenocarcinoma during AOM-induced colon carcinogenesis, and the PPE treatment partially prevented the loss of RXR{alpha} expression in high-grade dysplastic ACF. Taken together, our results strongly suggest the colon cancer preventive activity of PPE and identified possible molecular markers for future colon cancer prevention studies.

Key Words: aberrant crypt foci • tea polyphenols • high-grade dysplasia • colorectal cancer

* Authors contributed equally to this manuscript.

Received July 8, 2007; revised August 31, 2007; accepted September 9, 2007.


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