title: Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder carcinoma cells.
abstract: OBJECTIVE
  Capsaicin is a specialized agonist of transient receptor potential vanilloid type 1 Ca2(+) channel, a member of the vanilloid receptor family of cation channels. We aimed to investigate the effects of capsaicin on the proliferation and cell death of human bladder cancer cells.
  
  
  METHODS
  Human bladder cancer cell line 5637 was cultured and the expression of transient receptor potential vanilloid type 1 verified by immunofluorescence and Western blot. Cells were given different disposals (different capsaicin concentration with/without pre-treating with capsazepine; capsazepine, acting as a competitive antagonist of capsaicin) to observe cell viability, cell cycle and cell death by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry. The apoptosis indexes, such as intracellular production of reactive oxygen species and mitochondrial membrane potential were assessed to elucidate the potential mechanism of capsaicin effects in the cells.
  
  
  RESULTS
  Capsaicin decreased the viability of 5637 cells in a dose-dependent way. The flow cytometry outcome showed that capsaicin blocked the cell cycle in the G0/G1 period. The Western blot of cyclin-dependent-kinase involved in G1/S transfer verified this. Meanwhile, increased reactive oxygen species production and decreased mitochondrial membrane potential were detected in capsaicin-treated groups.
  
  
  CONCLUSIONS
  Capsaicin induces cell death through increased reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, capsaicin inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with the inhibition of CDK2, CDK4 and CDK6.
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yang
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guanbin
authors.initials: G
authors.lastname: Zhu
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000187:drug effects* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000187:drug effects* / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000187:drug effects* / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D002211:Capsaicin