Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan-1.
Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit the growth of a variety of cultured cells in a dose-dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined using an MTT assay and an in vivo tumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P < 0.05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.
Ohta
T
T
Department of Surgery, School of Medicine, Kanazawa University, Japan.
Arakawa
H
H
Futagami
F
F
Fushida
S
S
Kitagawa
H
H
Kayahara
M
M
Nagakawa
T
T
Miwa
K
K
Kurashima
K
K
Numata
M
M
Kitamura
Y
Y
Terada
T
T
Ohkuma
S
S
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D018942:Macrolides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases