Figure 1

Correlation between cell-type specific expression of anti-apoptotic Bcl-2 family proteins and synergistic combinational effects of ABTs and UNBS1450 in AML cells. (a) Analysis of major anti-apoptotic Bcl-2 proteins in AML cell lines. Chronic myeloid leukemia (CML) K562 cells were used for comparative studies. (b) Susceptibility to ABTs and UNBS1450 after 24 h incubation. IC50 values determined by mitochondrial membrane potential loss and quantification of apoptotic nuclear morphology. (c) Effect of significant protein expression levels (β-actin ratios) on IC50 for ABT-199 (μm) and UNBS1450 (nm). The larger the size, the larger IC50. Coefficients estimated from multiple regression equations (right), *P<0.05; **P<0.01. (d) Synergistic effects of subtoxic concentrations of ABTs (0.1 μm) and UNBS1450 (20 nm) in U937 cells assessed as described, together with western blot analysis of caspase cleavage in parallel to modulation of anti-apoptotic Bcl-2 proteins. (e) TF-1 cells treated at indicated concentrations of UNBS1450. Combinational index (CI) was estimated by Calcusyn software (Biosoft, Cambridge, UK). Data are the mean of at least three independent experiments±s.d. Significance was estimated by using two-way anaylsis of variance test (post hoc analyses, Dunnett). Significance is reported as ****P<0.0001, ####P<0.0001.