Carcinogenesis Advance Access originally published online on July 17, 2007
Carcinogenesis 2007 28(9):1978-1984; doi:10.1093/carcin/bgm161
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Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29203, USA
1 Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29245, USA
2 Department of Epidemiology and Biostatistics, School of Public Health
3 Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Columbia, SC 29208, USA
* To whom correspondence should be addressed at Cancer Chemoprevention Program, Hollings Cancer Center, 86 Jonathan Lucas Street, PO Box 250955, Charleston, SC 29245, USA. Tel: +843 792 7604; Fax: +843 792 3200; Email: wargovic{at}musc.edu
One of the liabilities of the ApcMin mouse as a model for colon cancer is its lack of a robust tumor response in the large bowel. In our protocol, we treated the ApcMin mouse with azoxymethane, a colon-selective carcinogen. This protocol induced a 4-fold increase in the number of colon tumors. We utilized this protocol to investigate the possible mechanisms of inhibition of colorectal carcinogenesis by green tea. Mice received water or a 0.6% (w/v) solution of green tea as the only source of beverage. Green tea treatment commenced at the eighth week of age and lasted for either 4 or 8 weeks. Green tea significantly inhibited the formation of new adenomas, but was ineffective against larger tumors. Mechanistically, we investigated the effects of green tea on the expression of biomarkers involved in colon carcinogenesis. Western blotting analysis showed that green tea decreased the total levels of the early carcinogenesis biomarker ß-catenin and its downstream target cyclin D1. In contrast, the expression of COX-2 was not altered. Immunohistochemical analysis showed that green tea inhibited the formation of adenomas overexpressing ß-catenin and cyclin D1, but did not reduce the number of COX-2-expressing adenomas. Our results suggest that green tea specifically targets initial stages of colon carcinogenesis; the time of administration of green tea is pivotal for effective chemoprevention. Beverage levels of green tea do not inhibit the progress of any large adenomas or adenocarcinomas existing prior to the tea administration.
Abbreviations: AOM, azoxymethane; EGCG, (–)-epigallocatechin gallate
Received May 16, 2006; revised June 29, 2007; accepted June 29, 2007.