Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis |
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| Authors: | Susanne M. Henning Piwen Wang Jonathan Said Clara Magyar Brandon Castor Ngan Doan Carmen Tosity Aune Moro Kun Gao Luyi Li David Heber |
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| Affiliation: | 1. Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;2. Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;1. Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea;2. Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Interdisciplinary Program for Bioinformatics, and Program for Cancer Biology, Seoul National University, Seoul, Republic of Korea;3. From the Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555 and;4. the Department of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219;1. Wuxi Medical School, Jiangnan University, Wuxi 214122, PR China;2. The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, PR China;3. School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China;1. Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK;2. The Dermatology Centre, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK;3. Department of Hematology and Immunology, Medical Faculty, Umm Al-Qura University, Mecca, Saudi Arabia;4. Institute of Child Health, Molecular and Cellular Immunology Unit, UCL, London, UK;5. Department of Histopathology, the Christie NHS Foundation Trust, Christie Hospital, Manchester, UK;1. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli studi di Palermo, Via Archirafi, 32, 90123 Palermo, Italy;2. Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Laboratorio di Biochimica, Università degli Studi di Palermo, via del Vespro 129, 90127 Palermo, Italy |
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| 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. |
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