Involvement of cytochrome c and caspases in apoptotic cell death of human submandibular gland ductal cells induced by concanamycin A.
In the present study, we found that a specific inhibitor of vacuolar type H+-ATPase (V-ATPase), concanamycin A, induced apoptosis in a human submandibular gland ductal cancer cell line, HSG. Immunoblot analysis revealed that cytochrome c was released from mitochondria into the cytoplasm when HSG cells were cultured with concanamycin A for 6 h. The maximum activities of caspase-3 and -9 were reached in HSG cells after 18 and 12 h culture of concanamycin A, respectively. Both caspase-3 and -9 were cleaved to an active form in HSG cells cultured with concanamycin A. Interestingly, concanamycin A decreased the level of heat shock protein 27 (HSP27) in HSG cells. Taken together, these findings suggest that apoptosis in HSG cells induced by concanamycin A is regulated by cytochrome c released from mitochondria into cytoplasm and the subsequent activation of caspases, and that HSP27 may interfere with caspase-dependent apoptotic cell death induced by concanamycin A.
Aiko
Katsuya
K
Department of Oral Microbiology, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580, Japan.
Tsujisawa
Toshiyuki
T
Koseki
Takeyoshi
T
Hashimoto
Shinichi
S
Morimoto
Yasuhiro
Y
Amagasa
Teruo
T
Nishihara
Tatsuji
T
D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D003574:Cytochrome c Group / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response; D006801:Humans; D007700:Kinetics; D018942:Macrolides; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018942:Macrolides; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C036978:concanamycin A; D020169:Caspases; D025262:Vacuolar Proton-Translocating ATPases