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: Susanne M Henning, Piwen Wang, Jonathan Said, Clara Magyar, Brandon Castor, Ngan Doan, Carmen Tosity, Aune Moro, Kun Gao, Luyi Li, David Heber
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 23 Issue 11 Pg. 1537-42 (Nov 2012) ISSN: 1873-4847 [Electronic] United States
• PMID: 22405694 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Hypoxia-Inducible Factor 1
• Plant Extracts
• Polyphenols
• 8-Hydroxy-2'-Deoxyguanosine
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Camellia sinensis
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (genetics)
• Deoxyguanosine (analogs & derivatives, analysis, metabolism)
• Humans
• Hypoxia-Inducible Factor 1 (metabolism)
• Macrophages (drug effects, pathology)
• Male
• Mice
• Mice, SCID
• Neovascularization, Pathologic (drug therapy)
• Oxidative Stress (drug effects)
• Plant Extracts (pharmacology)
• Polyphenols (pharmacokinetics, pharmacology)
• Prostatic Neoplasms (blood supply, drug therapy, metabolism)
• Xenograft Model Antitumor Assays