BAFILOMYCIN A(1) INDUCES APOPTOSIS IN THE HUMAN PANCREATIC-CANCER CELL-LINE CAPAN-1

Bafilomycin A(1), 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 ex amine whether bafilomycin A(1) inhibits the growth of Capan-1 human pa ncreatic cancer cells through apoptosis. The effect of bafilomycin A(1 ) on tumour growth in vitro and in vivo was examined using an MTT assa y and an in vivo tumour model. The presence or absence of apoptosis wa s determined by morphology and DNA analysis of tumour cells, The conce ntration of bafilomycin A(1) for 50 per cent inhibition of cell viabil ity during 72 h by the MTT assay was 5 nM, In DNA analysis, a ladder o f fragmented DNA was detected in Capan-1 cells treated,vith bafilomyci n A(1) at concentrations greater than 10 nM for 24 h. Nude mice bearin g a xenografted Capan-1 cell line tumour received 4 weeks of bafilomyc in A(1) (1.0 mg/kg per day), This treatment significantly inhibited tu mour growth compared with controls after 21 days (P<0.05). Histopathol ogical examination of tumour cells in the treated group demonstrated s igns of apoptosis: with chromatin condensation and cell shrinkage. The se observations suggest that bafilomycin A(1) inhibits the growth of C apan-1 human pancreatic cancer cells through apoptosis, (C) 1998 John Wiley & Sons, Ltd.