title: Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T-24 cells via blocking cell cycle progression and inducing apoptosis.
abstract: BACKGROUND
  Apigenin is a nontoxic dietary flavonoid, and it may have chemopreventive and therapeutic potential as an anti-inflammatory, antioxidant, and anti-cancer agent. However, its role in bladder cancer remains poorly understood. The aim of this study was to investigate the anti-proliferative activity of apigenin in human bladder cancer T-24 cells.
  
  
  RESULTS
  Apigenin inhibited T-24 cell proliferation in a dose-dependent manner. We demonstrated that apigenin-induced early and mid-apoptotic cell could be identified by Annexnin V-Alexa Fluor 488/PI apoptosis detection and TUNEL assay. Moreover, using a JC-1 staining assay, we found that apigenin may induce the loss of the mitochondrial membrane potential. By performing flow cytometry and Western blotting, apigenin-mediated subG1 phase acculmulation was also associated with an increase in the phospho-p53, p53, p21, and p27 levels, and with a decrease in the Cyclin A, Cyclin B1, Cyclin E, CDK2, Cdc2, and Cdc25C levels, thereby blocking cell cycle progression. ELISA showed that the subG1 phase acculmulation was due to the increase in the p53, p21, and p27 levels. In addition, apigenin increased the Bax, Bad, and Bak levels, but reduced the Bcl-xL, Bcl-2, and Mcl-1 levels, and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9, caspase-3, caspase-7, and PARP). Further analysis demonstrated that apigenin increased the ROS levels and depleted GSH in T-24 cells at 12 h.
  
  
  CONCLUSIONS
  The results suggested that apigenin inhibits T-24 cells proliferation via blocking cell cycle progression and inducing apoptosis. In addition, we discovered a potential anticancer activity of apigenin against T-24 cells.
authors: Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, 71051 Taiwan ; Department of Medical Laboratory Science and Biotechnology and Graduate Institute of Biological Technology, Chung Hwa University of Medical Technology, Tainan, 71703 Taiwan.
authors: Ming-Der
authors: MD
authors: Shi
authors: Department of Chest Medicine, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, 71051 Taiwan.
authors: Cheng-Kai
authors: CK
authors: Shiao
authors: Department of Nursing, Chung Hwa University of Medical Technology, Tainan, 71703 Taiwan.
authors: Yi-Chieh
authors: YC
authors: Lee
authors: Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, 71703 Taiwan ; Department of Biological Science and Technology and Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, 71703 Taiwan.
authors: Yuan-Wei
authors: YW
authors: Shih
keywords: Apigenin; CDK; Caspase; Cyclin; Mitochondrial membrane potential