title: Bee venom induces apoptosis through intracellular Ca2+ -modulated intrinsic death pathway in human bladder cancer cells.
abstract: OBJECTIVE
  To focus on bee venom-induced apoptosis in human bladder cancer TSGH-8301 cells and to investigate its signaling pathway to ascertain whether intracellular calcium iron (Ca(2+)) is involved in this effect.
  
  
  METHODS
  Bee venom-induced cytotoxic effects, productions of reactive oxygen species and Ca(2+) and the level of mitochondrial membrane potential (ΔΨm) were analyzed by flow cytometry. Apoptosis-associated proteins were examined by Western blot analysis and confocal laser microscopy.
  
  
  RESULTS
  Bee venom-induced cell morphological changes and decreased cell viability through the induction of apoptosis in TSGH-8301 cell were found. Bee venom promoted the protein levels of Bax, caspase-9, caspase-3 and endonuclease G. The enhancements of endoplasmic reticulum stress-related protein levels were shown in bee venom-provoked apoptosis of TSGH-8301 cells. Bee venom promoted the activities of caspase-3, caspase-8, and caspase-9, increased Ca(2+) release and decreased the level of ΔΨm. Co-localization of immunofluorescence analysis showed the releases of endonuclease G and apoptosis-inducing factor trafficking to nuclei for bee venom-mediated apoptosis. The images revealed evidence of nuclear condensation and formation of apoptotic bodies by 4',6-diamidino-2-phenylindole staining and DNA gel electrophoresis showed the DNA fragmentation in TSGH-8301 cells.
  
  
  CONCLUSIONS
  Bee venom treatment induces both caspase-dependent and caspase-independent apoptotic death through intracellular Ca(2+) -modulated intrinsic death pathway in TSGH-8301 cells.
authors.affiliation: Department of Nutrition, China Medical, Taipei, Taiwan.
authors.forename: Siu-Wan
authors.initials: SW
authors.lastname: Ip
authors.forename: Yung-Lin
authors.initials: YL
authors.lastname: Chu
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Heng-Chien
authors.initials: HC
authors.lastname: Ho
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Tung-Yuan
authors.initials: TY
authors.lastname: Lai
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001514:Bee Venoms / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D001514:Bee Venoms; D004706:Endodeoxyribonucleases; C052391:endonuclease G; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002118:Calcium