Green and black tea together represent the most commonly consumed beverages worldwide and is one of very few sources of phytochemicals with a broad chemopreventive activity against carcinogenesis. This activity and the lack of toxicity make tea an attractive agent for potential use in the reduction of human cancer risk. Consumption of green tea reduces risk for several cancers including lung, stomach, and pancreatic cancer. Recently it has been shown that habitual consumption of tea is associated with a reduced risk for colon cancer in a U.S. population. Nevertheless, much more research is needed before we can fully understand the cancer chemopreventive activities of tea and the possible application of tea in human cancer prevention. The overall goal of this project is to understand tea and cancer prevention by elucidating the mechanisms and identifying the active components involved. The Apc Min/+ mouse animal model for colon cancer and related cell lines will be used. This project will develop useful biomarkers, new agents (metabolites or analogs of the active components), and effective dosage forms for the prevention of human cancer. Specifically, we intend to test the hypothesis that orally administered tea is an effective inhibitor of carcinogenesis. The Min mouse and azoxymethane (AOM)-treated Min mouse will be used as the animal models to conduct dose-response studies for the effect of tea on aberrant crypt foci and colon tumor formation. Possible differences between green tea and black tea and the effect of caffeine on colon tumorigenesis will be assessed. We next will determine the effect of green tea and black tea on the proliferation and apoptosis of cells in the colon and correlate it with the tumorigenesis results. To study the molecular mechanisms, tea will be tested for its ability to modulate AP-l, ERK, JNK, c-Jun, j3-catenin and other proteins in the colons of Min mice. To elucidate the mechanistic basis for the inhibition of colon turnorigenesis by green tea and black tea in the Min and AOMIMin mouse models studies on arachidonic acid metabolism, cyclooxygenase (COX) protein and mRNA levels, and activities of COX, lipoxygenase, and phospholipase A2 will be conducted with colon samples. Furthermore, studies examining the effect of tea polyphenols on the growth of human colon adenocarcinoma cells that have high levels of COX-2 expression will be conducted.
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