title: Realgar-induced apoptosis of cervical cancer cell line Siha via cytochrome c release and caspase-3 and caspase-9 activation.
abstract: OBJECTIVE
  To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells.
  
  
  METHODS
  The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method.
  
  
  RESULTS
  Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar.
  
  
  CONCLUSIONS
  The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.
authors.affiliation: Department of Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yan-xiang
authors.initials: YX
authors.lastname: Cheng
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Bing-shu
authors.initials: BS
authors.lastname: Li
authors.forename: Xue-xian
authors.initials: XX
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fu
authors.forename: De-min
authors.initials: DM
authors.lastname: Pu
authors.forename: Li
authors.initials: L
authors.lastname: Hong
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D013440:Sulfides / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D001152:Arsenicals; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D013440:Sulfides; C058317:arsenic disulfide; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9