Inhibitors of vacuolar-type H(+)-ATPase suppresses proliferation of cultured cells.
We investigated effects of bafilomycin A1, 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 A1 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 A1, also inhibited strongly V-ATPase 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.
Manabe
T
T
Department of Physiology, Kansai Medical University, Osaka, Japan.
Yoshimori
T
T
Henomatsu
N
N
Tashiro
Y
Y
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002645:Chickens; D006801:Humans; D018942:Macrolides; D051379:Mice; D009928:Organ Specificity; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D051381:Rats; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases; D014617:Vacuoles / Q000201:enzymology*
D000900:Anti-Bacterial Agents; D018942:Macrolides; C057620:bafilomycin A; C036978:concanamycin A; D000251:Adenosine Triphosphatases; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases