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Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model
Ala Y Issa1, Suresh R Volate, Stephanie J Muga
1Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29203, USA.
Abstract:
One of the liabilities of the Apc(Min) 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 Apc(Min) 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 beta-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 beta-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.
Insights
Green tea effectively inhibits early-stage colon cancer development in mice by targeting beta-catenin and cyclin D1. However, it does not impact existing larger tumors, highlighting the importance of early intervention for chemoprevention.
Area of Science:
- Oncology
- Chemoprevention
- Gastroenterology
Background:
- The Apc(Min) mouse model has limitations in mimicking human colon cancer due to insufficient tumor development in the large bowel.
- Azoxymethane, a colon-specific carcinogen, was used to enhance tumor formation in Apc(Min) mice, creating a more robust model for colorectal carcinogenesis studies.
Purpose of the Study:
- To investigate the potential inhibitory mechanisms of green tea on colorectal carcinogenesis.
- To evaluate the effect of green tea on the expression of key biomarkers involved in colon cancer development.
Main Methods:
- Apc(Min) mice were treated with azoxymethane to induce colon tumors.
- Mice received either water or a 0.6% green tea solution as their sole beverage for 4 or 8 weeks.
- Western blotting and immunohistochemical analyses were performed to assess biomarkers such as beta-catenin, cyclin D1, and COX-2.
Main Results:
- Green tea significantly reduced the formation of new adenomas but was ineffective against pre-existing larger tumors.
- Green tea consumption decreased the expression of beta-catenin and cyclin D1, early biomarkers of carcinogenesis.
- The expression of COX-2 was not significantly altered by green tea treatment.
Conclusions:
- Green tea exhibits chemopreventive effects by targeting the initial stages of colon carcinogenesis, specifically influencing beta-catenin and cyclin D1 pathways.
- The timing of green tea administration is crucial for its efficacy in preventing colorectal cancer.
- Green tea is not effective in inhibiting the progression of established adenomas or adenocarcinomas.

