title: Specific inhibitors of vacuolar type H(+)-ATPases induce apoptotic cell death.
abstract: Concanamycin A and bafilomycin A1 are known as strong inhibitors of the vacuolar type H(+)-ATPases in vitro. These inhibitors exhibited cytotoxic effects on twelve cell lines in cell viability assay. On the other hand, the F1F0-type H(+)-ATPase inhibitor oligomycin and the E1E2-type H(+)-ATPase inhibitor vanadate showed no cytotoxic effect. We show here that concanamycin A and bafilomycin A1 induce a significant increase in the proportion of fragmented DNA in agarose gel electrophoresis. Flow cytometric cell cycle analysis of WEHI 231 cells stimulated with concanamycin A revealed the increased percentage of apoptotic cells with hypodiploid DNA. These findings indicate that cell death induced by specific inhibitors of vacuolar type H(+)-ATPases occurs through apoptosis.
authors.affiliation: Department of Oral Science, National Institute of Health, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
authors.forename: S
authors.initials: S
authors.lastname: Akifusa
authors.forename: T
authors.initials: T
authors.lastname: Koseki
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Muro
authors.forename: N
authors.initials: N
authors.lastname: Hanada
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D018942:Macrolides; D051379:Mice; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000201:enzymology*
chemical_list: D000900:Anti-Bacterial Agents; D004273:DNA, Neoplasm; D018942:Macrolides; C036978:concanamycin A; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases