SPECIFIC INHIBITORS OF VACUOLAR-TYPE H+-ATPASES INDUCE APOPTOTIC CELL-DEATH

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 Al induce a significant increase in the proportion of fragmented DNA in agarose get 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. (C) 1995 Academic Press, Inc.