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.

Abstract

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.

• Authors: Jing Li, Yongyi Cheng, Weixing Qu, Yi Sun, Zhiping Wang, Hanzhang Wang, Binqiang Tian
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 108 Issue 2 Pg. 84-93 (Feb 2011) ISSN: 1742-7843 [Electronic] England
• PMID: 21054790 (Publication Type: Journal Article)
• Copyright: © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

Chemical References

• Apoptosis Regulatory Proteins
• Flavonoids
• Flavonols
• NF-kappa B
• bcl-2-Associated X Protein
• fisetin

Topics

• Apoptosis
• Apoptosis Regulatory Proteins (pharmacology)
• Blotting, Western
• Cell Cycle
• Cell Line, Tumor
• Cell Proliferation
• Down-Regulation
• Flavonoids (pharmacology)
• Flavonols
• G1 Phase
• Genes, p53
• Humans
• Mitochondria (metabolism)
• NF-kappa B (metabolism)
• Resting Phase, Cell Cycle
• Signal Transduction
• Up-Regulation
• Urinary Bladder Neoplasms (metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)