In bafilomycin A1-resistant cells, bafilomycin A1 raised lysosomal pH and both prodigiosins and concanamycin A inhibited growth through apoptosis

AbstractIn bafilomycin A1-resistant cells (Vero-317 and MC-3T3-E1), bafilomycin A1 neither inhibited cell growth, induced cell death, nor activated caspase-3. However, 100 nM bafilomycin A1 did raise the lysosomal pH similar to 10 mM NH4Cl. Prodigiosins, H+/Cl− symporters that raise the lysosomal pH, inhibited cell growth through apoptosis and caused the activation of caspase-3. Concanamycin A also inhibited the growth of these cells through apoptosis. 10 mM NH4Cl inhibited the growth of these cells as well, but cytostatically. These results suggest that plecomacrolides inhibited cell growth apoptotically through specific site(s), in contrast to the cytostatic effect of 10 mM NH4Cl, besides raising the lysosomal pH