American Society of Hematology

Figure 5.

$Figure 5. CPS45 shows selective redox-dependent killing of transformed leukemic cells and acts in synergy with parthenolide to promote cell death. (A) Jurkat cells (left panels) and donor PBMCs (right panels) were incubated with increasing concentrations of CPS11, CPS45, CPS49 (1 nM-10 μM), and thalidomide (1 nM-200 μM). Viability was measured after 8, 16, and 32 hours of incubation by MTT assay. (B) Jurkat (left panels) and donor PBMCs (right panels) were incubated with either 5 μM CPS45 (top row) or CPS49 (bottom row) alone or with 20 and 40 μM NAC. Viability was determined after 8 hours. (C) PBMCs, PBMC blasts, and 15 different transformed cell lines (Table S1) were treated with increasing doses of CPS45 for 16 hours. Viability was determined by MTT and analyzed by hierarchical clustering (Euclidean distance, average linkage). (D) HeLa cells were preincubated with 0, 25, or 50 μM BSO for 24 hours prior to treatment with the indicated concentration of CPS45 for 16 hours. (E) Left panel shows Jurkat cells were incubated with increasing concentrations (31.25 nM-2 μM) of CPS45 and parthenolide at a fixed ratio (1:2.5) for 24 hours. Viability was measured by MTT assay and CI values for each fractional effect (right panel) were calculated using commercially available software (Calcusyn; Biosoft). CI values less than 1.0 correspond to synergistic interactions. Error bars represent SEM.$

CPS45 shows selective redox-dependent killing of transformed leukemic cells and acts in synergy with parthenolide to promote cell death. (A) Jurkat cells (left panels) and donor PBMCs (right panels) were incubated with increasing concentrations of CPS11, CPS45, CPS49 (1 nM-10 μM), and thalidomide (1 nM-200 μM). Viability was measured after 8, 16, and 32 hours of incubation by MTT assay. (B) Jurkat (left panels) and donor PBMCs (right panels) were incubated with either 5 μM CPS45 (top row) or CPS49 (bottom row) alone or with 20 and 40 μM NAC. Viability was determined after 8 hours. (C) PBMCs, PBMC blasts, and 15 different transformed cell lines (Table S1) were treated with increasing doses of CPS45 for 16 hours. Viability was determined by MTT and analyzed by hierarchical clustering (Euclidean distance, average linkage). (D) HeLa cells were preincubated with 0, 25, or 50 μM BSO for 24 hours prior to treatment with the indicated concentration of CPS45 for 16 hours. (E) Left panel shows Jurkat cells were incubated with increasing concentrations (31.25 nM-2 μM) of CPS45 and parthenolide at a fixed ratio (1:2.5) for 24 hours. Viability was measured by MTT assay and CI values for each fractional effect (right panel) were calculated using commercially available software (Calcusyn; Biosoft). CI values less than 1.0 correspond to synergistic interactions. Error bars represent SEM.

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