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.
Highlights
Green tea is known to have health-promoting effects that are attributed to catechin polyphenols, which have anti-inflammatory and -oxidative properties [1, 2]
Tumor invasion was associated with increased tumor size (OR = 84.33, 95% confidence intervals (CIs) = 12.84–554.0, P < 0.001), high Microvessel density (MVD) (OR = 15.96, 95% CI = 3.99–63.85, P < 0.001), high proliferation index (PI) (OR = 27.50, 95% CI = 6.06–124.8, P < 0.001), and upregulation of COX-2 (OR = 5.18, 95% CI = 1.48–18.19, P = 0.010), vascular endothelial growth factor (VEGF)-A (OR = 15.96, 95% CI = 3.99–63.85, P < 0.001), and HO-1 (OR = 6.08, 95% CI = 1.72–21.50, P = 0.005) expression
The present study investigated changes in HuR expression following green tea polyphenol (GTP) intake in bladder cancer, based on the findings that HuR expression is positively associated with tumor
Summary
Green tea is known to have health-promoting effects that are attributed to catechin polyphenols, which have anti-inflammatory and -oxidative properties [1, 2]. Many studies have demonstrated the anti-cancer effects of green tea polyphenol (GTP) in a variety of malignancies [3, 4, 5], and epidemiologic studies have shown that green tea consumption reduces cancer risk. Green Tea Polyphenol and Cancer-Related Factors in an Animal Model of Bladder Cancer [6]. New cancer treatment strategies in combination with GTP intake have been recommended for several types of cancer [7, 8]. The anti-cancer effects of GTP have been linked to the regulation of various cancer-related molecules [9, 10]. The mechanism underlying these effects is not well understood
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