Synergistic and sequence-dependent interaction between radiation and AT-101 in U937 cells. A: The combination of radiation and AT-101 induces more apoptosis than the sum of the effects caused by the single agent treatment. Hatched bars represent the apoptotic effect by AT-101 alone (0-2 μM); black bars represent the combined effect with radiation (8 Gy). B: Isobolographic analysis of the combined effect of 40.6% apoptosis (* in A) induced by 0.4 μM AT-101 and 8 Gy radiation. The combination point is projected below the area of additivity, indicating synergy. The combination index for this point: CI = 0.42. C: Sequence-dependency of radiation and AT-101. Radiation (6 Gy) and AT-101 (1 μM) were either applied concurrently (hatched bars) or sequentially (AT-101 24 h after radiation; black bars). Apoptosis was analyzed at t = 24 h after AT-101. D: MTT cell viability assays in Jurkat T and U937 cells. AT-101 was added at the indicated concentrations (solid lines); radiation was dosed at 8 Gy (dashed line). Viability was determined at t = 48 h after radiation (i.e. 24 h after AT-101). Data presented in A, C and D are mean values (± SD) from 2 independent experiments.