title: Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization.
abstract: OBJECTIVE
  To investigate the effects of capsaicin (CAP) on proliferation of bladder cancer T24 cells in vitro as well as on xenografts in nude mice in vivo.
  
  
  METHODS
  T24 cells were assessed for cell viability and apoptosis by 3-(4, 5-dimethylthiazol-2-yl)-3, 5-diphenyltetrazolium bromide assay and flow cytometry analysis after incubation with different concentrations of CAP. To uncover the mechanism by which CAP affected the viability of T24 cells, intracellular production of reactive oxygen species (ROS) and mitochondrial membrane potential were assessed. To study the in vivo effects of CAP, T24 cells were grown as xenografts in nude mice and CAP (5 mg/kg by wt) was subcutaneously injected into nude mice with bladder tumors.
  
  
  RESULTS
  CAP decreased the viability of T24 cells in a dose-dependent manner without marked apoptosis. CAP induced ROS production and mitochondrial membrane depolarization, thereby inducing cell death, not apoptosis, in T24 cells at a concentration of 100 microM or higher. Furthermore, these effects of CAP could be reversed by capsazepine, the antagonist of transient receptor potential vanilloid type 1 channel. In vivo experiment showed that CAP significantly slowed the growth of T24 bladder cancer xenografts as measured by size (661.80 +/- 62.03 vs 567.02 +/- 43.94 mm(3); P <.01).
  
  
  CONCLUSIONS
  CAP mediates cell death in T24 cells through calcium entry-dependent ROS production and mitochondrial depolarization, and it may have a role in the management of bladder cancer.
authors: Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors: Zhong-Hua
authors: ZH
authors: Yang
authors: Xing-Huan
authors: XH
authors: Wang
authors: Huai-Peng
authors: HP
authors: Wang
authors: Li-Quan
authors: LQ
authors: Hu
authors: Xin-Min
authors: XM
authors: Zheng
authors: Shi-Wen
authors: SW
authors: Li
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D017382:Reactive Oxygen Species; D002211:Capsaicin