title: Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis.
abstract: It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice.
authors.affiliation: Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. shenning@mednet.ucla.edu
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.forename: Piwen
authors.initials: P
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Clara
authors.initials: C
authors.lastname: Magyar
authors.forename: Brandon
authors.initials: B
authors.lastname: Castor
authors.forename: Ngan
authors.initials: N
authors.lastname: Doan
authors.forename: Carmen
authors.initials: C
authors.lastname: Tosity
authors.forename: Aune
authors.initials: A
authors.lastname: Moro
authors.forename: Kun
authors.initials: K
authors.lastname: Gao
authors.forename: Luyi
authors.initials: L
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Heber
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D028241:Camellia sinensis; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000493:pharmacokinetics / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051793:Hypoxia-Inducible Factor 1; D010936:Plant Extracts; D059808:Polyphenols; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D003849:Deoxyguanosine