title: ATPase inhibitors suppress actinomycin D-induced apoptosis in leukemia cells.
abstract: BACKGROUND
  Apoptosis is mediated by many kinds of enzymes such as caspases, DNase and protein kinases. Recently, ATPase has been shown to be involved in the apoptotic system, but its role is not fully understood.
  
  
  METHODS
  We investigated the effect of 8 species of ATPase inhibitors on actinomycin D plus colcemid-induced apoptosis in human megakaryoblastic leukemia CMK-7 cells by monitoring caspase-3 activation and DNA cleavage.
  
  
  RESULTS
  2,3-Butanedione monoxime (BDM), lansoprazole, cyclopiazonic acid, geldanamycin and radicicol suppressed the apoptosis. Among these compounds, geldanamycin was the strongest suppressor of both caspase-3 activation and DNA cleavage. Furthermore, Western blotting showed that radicicol suppressed the proteolytic cleavage of procaspase-9 more strongly than BDM, lansoprazole or cyclopiazonic acid.
  
  
  CONCLUSIONS
  Since geldanamycin and radicicol are specific inhibitors of the ATPase in HSP90, the present result implies that ATPase activity in HSP90 plays some role in this apoptosis.
authors.affiliation: Research Institute of Biological Resources, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shiono
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Syuichi
authors.initials: S
authors.lastname: Oka
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamazaki
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D003609:Dactinomycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D064747:Lansoprazole; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D007211:Indoles; D064747:Lansoprazole; C004717:diacetylmonoxime; D003609:Dactinomycin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000251:Adenosine Triphosphatases; D003931:Diacetyl; D009853:Omeprazole; C000543:cyclopiazonic acid; D003703:Demecolcine