Sigma-2 ligands induce caspase-3 activation in pancreas cancer. Panc02 cells were pre-treated with caspase-3 inhibitor (DEVD-FMK 1 μM) or DMSO vehicle for one hour prior to exposure to sigma-2 ligands (25 μM) SV119, SW43, siramesine (SRM) or DMSO vehicle for 18 hours. A. Caspase-3 activation was quantified by cleavage of the fluorogenic substrate Ac-DEVD-AMC and expressed relative to vehicle. The caspase-3 specific inhibitor DEVD-FMK abrogates caspase-3 dependent cleavage. B. Caspase-3 inhibition does not protect cells from sigma-2 ligand induced cell death. C. Flow cytometry for Annexin-V verifies apoptosis by sigma-2 ligand. D. Representative flow cytometry dot plot showing cells moving from Annexin-V negative quadrant (upper panel) with vehicle towards Annexin-V positive quadrant (lower panel) with SW43 treatment. (Means ± SEM), n ≥ 3, *p < 0.05, **p > 0.05.