Fisetin, a Dietary Flavonoid, Induces Cell Cycle Arrest and Apoptosis through Activation of p53 and Inhibition of NF‐Kappa B Pathways in Bladder Cancer Cells

• Published in: Basic & clinical pharmacology & toxicology Vol. 108; no. 2; pp. 84 - 93
• Main Authors: Li, Jing, Cheng, Yongyi, Qu, Weixing, Sun, Yi, Wang, Zhiping, Wang, Hanzhang, Tian, Binqiang
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2011; Blackwell
• Subjects: Apoptosis; Apoptosis Regulatory Proteins - pharmacology; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Flavonoids - pharmacology; G1 Phase; Genes, p53; Humans; Medical sciences; Mitochondria - metabolism; Nephrology. Urinary tract diseases; NF-kappa B - metabolism; Pharmacology. Drug treatments; Resting Phase, Cell Cycle; Signal Transduction; Tumors of the urinary system; Up-Regulation; Urinary Bladder Neoplasms - metabolism; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urinary system disease; Nutrition; p53 Protein; Urinary tract disease; Malignant tumor; Bladder cancer; Flavonoid; Feeding; Polyphenol; TP53 Gene; Diet; Cell death; Cell cycle; Phenols; Bladder disease; Inhibitor; Tumor cell; Cancer; Apoptosis; Tumor suppressor gene
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/j.1742-7843.2010.00613.x

:  There is an obvious urgent need to find effective and safe therapies to prevent both recurrence and progression of bladder cancer. In the present study, we report that fisetin‐induced apoptosis in human bladder cancer is mediated via modulation of two related pathways: up‐regulation of p53 and down‐regulation of NF‐kappa B activity, causing a change in the ratio of pro‐ and anti‐apoptotic proteins. The results showed that fisetin inhibited the proliferation of T24 and EJ cells by inducing apoptosis and blocking cell cycle progression in the G0/G1 phase. Western blot assay showed that fisetin significantly increases the expression of p53 and p21 proteins, and decreases the levels of cyclin D1, cyclin A, CDK4 and CDK2, thereby contributing to cell cycle arrest. In addition, fisetin increased the expression of Bax and Bak but decreased the levels of Bcl‐2 and Bcl‐xL and subsequently triggered mitochondrial apoptotic pathway. Our study suggests that the activation of p53 and inhibition of the NF‐kappa B system may play important roles in the fisetin‐induced apoptosis in bladder cancer cells.