In bafilomycin A1-resistant cells, bafilomycin A1 raised lysosomal pH and both prodigiosins and concanamycin A inhibited growth through apoptosis.
In bafilomycin A(1)-resistant cells (Vero-317 and MC-3T3-E1), bafilomycin A(1) neither inhibited cell growth, induced cell death, nor activated caspase-3. However, 100 nM bafilomycin A(1) did raise the lysosomal pH similar to 10 mM NH(4)Cl. 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 NH(4)Cl 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 NH(4)Cl, besides raising the lysosomal pH.
Tanigaki
Keiji
K
Department of Dynamic Physiology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Takara-machi 13-1, Ishikawa 920-0934, Japan.
Sasaki
Satoshi
S
Ohkuma
Shoji
S
D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D018942:Macrolides; D051379:Mice; D011353:Prodigiosin / Q000494:pharmacology*; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D018942:Macrolides; C036978:concanamycin A; C040929:bafilomycin A1; D011353:Prodigiosin