We investigated effects of bafilomycin A,, a specific inhibitor of vacuolar-type H'-ATPase (V-ATPase), and its analogues on proliferation of various cultured cells. The proliferation of the various cell lines was suppressed by adding bafilomycin A, to the culture medium. This inhibitory effect appeared at a concentration of nanomolar order and was dose dependent. Although the suppression was reversible, the drug exerted not only suppression of the proliferation but also death to some cell lines. Drug concentration required for 50% inhibition of the cell proliferation during 48 h differed markedly depending on cell species and the sensitivity appears to increase by the transformation of the cells. Two derivatives of concanamycin A, an analogue of bafilomycin A,, also inhibited strongly V-AT-Pase in vitro and in vivo, and simultaneously cell proliferation. Two concanamycin A derivatives which have lost inhibitory effect on V-ATPase lost inhibitory effect on cell proliferation as well. These results suggest that V-ATPase is involved in the machinery maintaining the cell proliferation. 8 1993 Witey-Liss, Inc.
A family of H+-translocating ATPase (V-ATPase) is associated with several membrane organelles belonging to the biosynthetic and endocytic pathways (Nelson and Taiz, 1989). This new class of H+-ATPase, named vacuolar-type H'-ATPase (V-ATPase), has molecular structure and drug sensitivities distinct from FoF1-type ATPase in the mitochondria and El-E,-type ATPase in the plasma membranes. The function of V-ATPase is to pump protons into the organelles by hydrolyzing ATP.