The anticarcinogenic potential of green (GT) and black tea (BT) has been demonstrated in many animal and in vitro cell culture studies. Tea polyphenols, such as epigallocatechin gallate (EGCG) and theaflavins, inhibit cell growth through a variety of mechanisms such as antioxidant activity, alteration of redox-sensitive signal transduction pathways (nuclear factor-kappa B, activator protein 1, mitogen-activated protein kinase) and inhibition of insulin-like growth factor (IGF-1) leading to the inhibition of proliferation, induction of apoptosis, cell cycle arrest as well as inhibition of angiogenesis. However most cell culture and animal studies have been performed with higher concentrations than achievable in humans. It is not clear whether effects observed in animal and cell culture studies can be applied to human studies. Therefore, the overall goal of this study is to perform a phase II clinical intervention trial to investigate whether the consumption of a green tea supplement (Polyphenon E) equivalent to 6 cups of GT or 6 cups of BT for 8 weeks prior to prostatectomy will decrease oxidative stress, alter signaling pathways leading to an inhibition of proliferation and increase of apoptosis in the prostate. We will use immunohistochemistry to determine the apoptotic index and protein expression of Ki67, Bax, Bcl-2, NFkB and concentration of 8-hydroxydeoxyguanosine in sections of equal morphological changes of adenocarcinoma in the human prostate. Serum prostate specific antigen and IGF-1/IGFBP-3 will be determined using chemiluminescent analysis. Since in vivo polyphenols and theaflavins are subject to extensive endogenous and colonic metabolism we propose that metabolites contribute to the chemopreventive effect of GT and BT. We will use high performance liquid chromatography with coularray electrochemical detection as well as mass spectrorrietry (MS) and gas chromatography/ MS to determine the concentrations of polyphenols, theaflavins and six different endogenous and colonic metabo- lites in the prostate, serum and urine of the participants of our tea intervention trial. We will also use the serum collected before and after the tea intervention to be tested in our ex vivo bioassay in LNCaP prostate cancer cells. Finally we will determine the effect of the six metabolites on apoptosis, Bax/Bcl-2 and NFkB- DNA binding after tumor necrosis factor alpha stimulation in LNCaP cells. The results will assist in designing dietary supplements for chemoprevention of early stages of prostate cancer or during watchful waiting.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA116242-04
Application #
7738517
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Kim, Young S
Project Start
2007-02-01
Project End
2011-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
4
Fiscal Year
2010
Total Cost
$264,195
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Henning, Susanne M; Wang, Piwen; Said, Jonathan W et al. (2015) Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy. Prostate 75:550-9
Wang, Piwen; Vadgama, Jaydutt V; Said, Jonathan W et al. (2014) Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea. J Nutr Biochem 25:73-80
Henning, Susanne M; Wang, Piwen; Carpenter, Catherine L et al. (2013) Epigenetic effects of green tea polyphenols in cancer. Epigenomics 5:729-41
Henning, Susanne M; Wang, Piwen; Abgaryan, Narine et al. (2013) Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol Nutr Food Res 57:483-93
Wang, Piwen; Heber, David; Henning, Susanne M (2012) Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Nutr Cancer 64:580-7
Henning, Susanne M; Wang, Piwen; Said, Jonathan et al. (2012) Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis. J Nutr Biochem 23:1537-42
Henning, Susanne M; Wang, Piwen; Heber, David (2011) Chemopreventive effects of tea in prostate cancer: green tea versus black tea. Mol Nutr Food Res 55:905-20
Wang, Piwen; Aronson, William J; Huang, Min et al. (2010) Green tea polyphenols and metabolites in prostatectomy tissue: implications for cancer prevention. Cancer Prev Res (Phila) 3:985-93
Wang, Piwen; Henning, Susanne M; Heber, David (2010) Limitations of MTT and MTS-based assays for measurement of antiproliferative activity of green tea polyphenols. PLoS One 5:e10202
Aronson, William J; Barnard, R James; Freedland, Stephen J et al. (2010) Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer. J Urol 183:345-50

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