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Specific inhibitors of vacuolar type H(+)-ATPases induce apoptotic cell death.

Biochemical and biophysical research communications (1995-07-06)
T Nishihara, S Akifusa, T Koseki, S Kato, M Muro, N Hanada
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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.

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Concanamycin A, ≥70% (HPLC)
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Bafilomycin A1, InSolution, ≥90%, A macrolide antibiotic that acts as a specific inhibitor of vacuolar-type H+-ATPase
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