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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA096694-04
Application #
6923949
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Milner, John A
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
4
Fiscal Year
2005
Total Cost
$258,990
Indirect Cost
Name
University of South Carolina at Columbia
Department
Pathology
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Morris, Jay; Moseley, Vondina R; Cabang, April B et al. (2016) Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXR? expression in human colon cancer cells. Oncotarget 7:35313-26
Morris, Jay; Fang, Yuan; De Mukhopdhyay, Keya et al. (2016) Natural Agents Used in Chemoprevention of Aerodigestive and GI Cancers. Curr Pharmacol Rep 2:11-20
Knackstedt, Rebecca; Shaoli, Sun; Moseley, Vondina et al. (2014) The importance of the retinoid X receptor alpha in modulating inflammatory signaling in acute murine colitis. Dig Dis Sci 59:753-9
Knackstedt, Rebecca W; Moseley, Vondina R; Sun, Shaoli et al. (2013) Vitamin D receptor and retinoid X receptor * status and vitamin D insufficiency in models of murine colitis. Cancer Prev Res (Phila) 6:585-93
Moseley, Vondina R; Morris, Jay; Knackstedt, Rebecca W et al. (2013) Green tea polyphenol epigallocatechin 3-gallate, contributes to the degradation of DNMT3A and HDAC3 in HCT 116 human colon cancer cells. Anticancer Res 33:5325-33
Knackstedt, Rebecca W; Moseley, Vondina R; Wargovich, Michael J (2012) Epigenetic mechanisms underlying diet-sourced compounds in the prevention and treatment of gastrointestinal cancer. Anticancer Agents Med Chem 12:1203-10
Wargovich, Michael J; Morris, Jay; Brown, Vondina et al. (2010) Nutraceutical use in late-stage cancer. Cancer Metastasis Rev 29:503-10
Volate, Suresh R; Muga, Stephanie J; Issa, Ala Y et al. (2009) Epigenetic modulation of the retinoid X receptor alpha by green tea in the azoxymethane-Apc Min/+ mouse model of intestinal cancer. Mol Carcinog 48:920-33
Peng, Guang; Wargovich, Michael J; Dixon, Dan A (2006) Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells. Cancer Lett 238:260-70
Peng, Guang; Dixon, Dan A; Muga, Stephanie J et al. (2006) Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis. Mol Carcinog 45:309-19