The long-term goal of this project is to elucidate the mechanisms of inhibition of carcinogenesis by tea (Camellia sinensis) and to assess its usefulness in the prevention of human cancer. Previous studies have demonstrated that tea preparations inhibit carcinogenesis in animal models and that tea polyphenols inhibit cell transformation, proliferation, and related signal transduction pathways. Plasma and tissue levels of tea polyphenols and their metabolites in animals and humans have been determined. In this project the applicant and colleagues plan to further elucidate the mechanisms of action and identify the active components involved with the following specific aims: 1. To elucidate the mechanisms of inhibition of carcinogenesis by tea in the NNK-induced lung carcinogenesis model in A/J mice and in relevant cell lines. The applicant and colleagues will study the inhibition of cell proliferation and tumor promotion by tea and tea constituents, and relate the activity to pertinent signal transduction pathways (such as MAP-kinases and AP-1 activation) in short and long term animal experiments. In-depth mechanistic studies in cell lines, on the inhibition of AP-1 and NFkB and the upstream of protein kinase cascade, will complement the animal studies and provide basic understanding of the action of tea polyphenols in general. 2. To determine the blood, urine, and tissue levels of tea polyphenols and their metabolites in rodents and humans under different experimental conditions and to understand the factors influencing these levels. Improved methods will be developed to include the analysis of many newly identified metabolites in pharmacokinetic studies. The blood and tissue levels of these compounds will serve as a reference for evaluating the mechanisms of anti-carcinogenesis and for comparing results in mice and humans. 3. To synthesize and determine the biological activities of the metabolites identified in Aim 2 in cell lines and animal models. The applicant and colleagues will address key issues concerning the bioavailability and bioactivities of O-methyl, glucuronide, and sulfate derivatives and two ring-fission metabolites of tea catechins.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-ET-2 (01))
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Malone, Winfred F
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Rutgers University
Schools of Pharmacy
New Brunswick
United States
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Yang, Chung S; Zhang, Jinsong; Zhang, Le et al. (2016) Mechanisms of body weight reduction and metabolic syndrome alleviation by tea. Mol Nutr Food Res 60:160-74
Xiao, Hang; Zhang, Qiang; Lin, Yong et al. (2008) Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer 122:2115-24
Sang, Shengmin; Hou, Zhe; Lambert, Joshua D et al. (2005) Redox properties of tea polyphenols and related biological activities. Antioxid Redox Signal 7:1704-14
Yang, Chung S; Liao, Jie; Yang, Guang-yu et al. (2005) Inhibition of lung tumorigenesis by tea. Exp Lung Res 31:135-44
Hou, Zhe; Sang, Shengmin; You, Hui et al. (2005) Mechanism of action of (-)-epigallocatechin-3-gallate: auto-oxidation-dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells. Cancer Res 65:8049-56
Sun, Can-Lan; Yuan, Jian-Min; Wang, Xue-Li et al. (2004) Dietary soy and increased risk of bladder cancer: a prospective cohort study of men in Shanghai, China. Int J Cancer 112:319-23
Liao, Jie; Yang, Guang-Yu; Park, Eon Sub et al. (2004) Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea. Nutr Cancer 48:44-53
Lu, Hong; Meng, Xiaofeng; Li, Chuan et al. (2003) Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab Dispos 31:452-61
Lu, Hong; Meng, Xiaofeng; Yang, Chung S (2003) Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (-)-epigallocatechin gallate. Drug Metab Dispos 31:572-9
Lambert, Joshua D; Yang, Chung S (2003) Mechanisms of cancer prevention by tea constituents. J Nutr 133:3262S-3267S

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