Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization.
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.
Yang
Zhong-Hua
ZH
Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, China.
Wang
Xing-Huan
XH
Wang
Huai-Peng
HP
Hu
Li-Quan
LQ
Zheng
Xin-Min
XM
Li
Shi-Wen
SW
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*
D017382:Reactive Oxygen Species; D002211:Capsaicin