title: Green Tea Polyphenol Induces Changes in Cancer-Related Factors in an Animal Model of Bladder Cancer.
abstract: Green tea polyphenol (GTP) suppresses carcinogenesis and aggressiveness in many types of malignancies including bladder cancer. However, the mechanistic basis of these effects is not well understood. This was investigated in the present study using a mouse model of chemically induced bladder cancer. C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14-24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation and microvessel density were evaluated along with immunohistochemical analysis of human antigen (Hu)R, vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. Nuclear HuR expression was not associated with any parameters such as carcinogenesis, muscle invasion, and GTP intake. These results indicate that GTP intake can suppress tumor progression and malignant behavior in an animal model of bladder cancer. We also speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer.
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miyata
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asai
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sagara
authors.affiliation: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Bungo
authors.initials: B
authors.lastname: Furusato
authors.affiliation: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.affiliation: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D000067780:ELAV-Like Protein 1 / Q000378:metabolism; D005260:Female; D051379:Mice; D059808:Polyphenols / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000067780:ELAV-Like Protein 1; D059808:Polyphenols; D013662:Tea