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Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine-induced bladder cancer
Authors:Yuji Sagara  Yasuyoshi Miyata  Koichiro Nomata  Tomayoshi Hayashi  Hiroshi Kanetake
Institution:1. Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;2. Department of Urology, Nagasaki Municipal Hospital, Nagasaki, Japan;3. Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan;1. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong;2. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong;3. Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong;4. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong;5. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong;1. Institute of Biochemistry I ? Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany;2. Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;3. Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe‐University Frankfurt, Theodor‐Stern‐Kai 7, 60590 Frankfurt am Main, Germany;1. Pharmacology/Toxicology Department, Basic Pharmaceutical Sciences Division, College of Pharmacy and Pharmaceutical Science, Florida A&M University, Tallahassee, FL 32307, United States;2. Global Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, United States;3. Environmental Agricultural and Occupational Health Department, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, United States;4. Pharmacology/Toxicology Department, Basic Pharmaceutical Sciences Department, College of Pharmacy and Pharmaceutical Science, Florida A&M University, Tallahassee, FL 32307, United States;1. School of Nursing, College of Medicine, Chang Gung University, No. 259, Wen-hwa 1st Road, Kwei-shan, Taoyuan 333, Taiwan, ROC;2. School of Nursing, College of Nursing, Taipei Medical University, 250, Wu-Xing Street, Taipei 110, Taiwan;3. Department of Nursing, Chang Gung University of Science and Technology, No. 261, Wen-hwa 1st Road, Kwei-shan, Taoyuan 33303, Taiwan;1. Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran;2. Department of Biosystems, Faculty of Bioscience Engineering, Katholieke Universiteit Leuven – KULeuven, Kasteelpark Arenberg 30, B-3001 Heverlee, Belgium;3. Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;4. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract:Background: Green tea polyphenol (GTP) suppresses malignancy in bladder cancer cell lines. However, the detail of its anti-carcinogenic effect in vivo is not fully understood. This study investigated the effect of GTP on bladder tumor size and angiogenesis in mice given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN), with and without GTP. Methods: Eight-week-old female C3H/He mice were treated with and without 0.05% BBN solution for 14 or 24 weeks. In addition, they were also treated with and without 0.5% GTP solution for the same periods. Histopathological diagnosis was established using hematoxylin and eosin staining, and microvessel density (MVD) was estimated by counting CD34- and von Willebrand factor-positive vessels in the tumor area. Results: At 14 weeks, cancer cells were detected in BBN and BBN + GTP mice 5/14 (35.7%) and 3/14 (21.4%), respectively, p = 0.678]. At 24 weeks, the incidence of cancer cells was also similar between the groups (BBN + GTP: 61.9% vs. BBN: 82.6%; p = 0.179). However, the frequency of invasive tumors in BBN + GTP mice was significantly lower (23.8%; p = 0.030) than in those given BBN alone (65.2%). Tumor volume and MVD of intratumoral and stromal region in the BBN + GTP group were also significantly lower than in BBN mice. Conclusion: The results showed that GTP had no anti-carcinogenic effect, but inhibited tumor growth and invasion in mice with established bladder cancer, at least in part through the regulation of angiogenesis. Our data suggest that GTP seems to suppress tumor development in bladder cancer.
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