XIAP antagonist induces caspase-9–mediated apoptosis in etoposide-resistant DLBCL-derived cell lines. (A) Dose-response curves of the DLBCL cell lines SUDHL4 (■), SUDHL5 (▴), and HT (♦) after 24 hours of exposure to XIAP antagonist 1396-12 (solid line) or the inactive compound 1396-28 (dashed line) are shown. (B) Detection of cell death in DLBCL cell lines untreated (----) or treated with 25 μM XIAP antagonist (—) or 500 nM etoposide (solid gray line) for increasing periods of time. (C) Cell death detected in DLBCL cell lines after treatment with 25 μM XIAP antagonist in combination with increasing concentrations of the pancaspase inhibitor z-VAD-fmk or the caspase-9 inhibitor LEHD-fmk for 16 hours. (■ indicates 25 μM 1396-12; ▩, 1396-12 + 50 μM zVAD-FMK; ▨, 1396-12 + 100 μM zVAD-FMK; □, 1396-12 + 50 μM LEHD-FMK; and ▧, 1396-12 + 100 μM LEHD-FMK). (D) XIAP antagonist induced caspase-3/7 activity in DLBCL cell lines SUDHL4 (■), SUDHL5 (▴), and HT (♦) after exposure to 25 μM XIAP antagonist for 24 hours. Nalm6 cells (●) treated with etoposide were used as positive control. Error bars represent SD of the mean value of 3 experiments. (E) Expression of Bax and cytosolic cytochrome c from a time-course treatment of SUDHL4 cells with 10 μM 1396-12.