Synergistic killing of DLBCL cells by the combined inhibition of GLS1 and BCL2. (A) DLBCL cells were treated for 48 hours with solvent, 0.5 μM ABT-199, or 250 nM CB-839 alone or in combination, with or without 100 μM α-tocopherol. Mitochondrial ROS were then quantified by flow cytometry. The percentage of MitoSOX-positive cells of CB-839–treated samples was normalized to the solvent control. (B) SU-DHL-4 and U2932 cells were treated with CB-839 alone (left panels) or in combination with ABT-199 (right panels). Cell survival was quantified by MTS assay after 48 hours, and combination treatments were normalized to the respective CB-839 single treatment. Statistical significance was calculated by comparing the data points of the solvent control with the CB839-treated samples in presence of 4 μM ABT-199. (C) The Loewe additivity model was used to identify synergism between the CB-839 and ABT-199 doses assayed. Error bars correspond to the mean ± SD. Data are representative of 3 for panels A-B independent experiments. Statistical significance was calculated using the Student t test (unpaired, 2-tailed) to compare the indicated samples. MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium.