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Fig. 4 | BMC Cancer

Fig. 4

From: Obatoclax is a direct and potent antagonist of membrane-restricted Mcl-1 and is synthetic lethal with treatment that induces Bim

Fig. 4

Obatoclax is active in cells whose survival depends on Mcl-1. a Viability of KMS-11 myeloma cells was measured in the presence of 0.5 μM and 1 μM obatoclax (gray bars) or the des-methoxy derivative of obatoclax (white bars) or vehicle (1 % DMSO) for 48 h. The % cell death was normalized to vehicle control. Error bars show the mean with SEM. b TE671 cells depend on both Mcl-1 and Bcl-XL for survival. Cells were transfected with the indicated combinations of siRNA for 48 h. Cell death was determined and expressed as percentage of cells treated with control siRNA (siCtl) (upper panel). Western blot analysis of the siRNA treated cells (lower panel). c Knocking down of Bcl-XL enhances death of TE671 cells by obatoclax. TE671 cells were transfected with control siRNA or Bcl-XL siRNA for 24 h followed by 48-hr treatment with 200 nM obatoclax. Cell death was determined and expressed as percentage of transfected cells treated with DMSO. d Obatoclax induced caspase activation in Tsc2+/−Eμ-Myc lymphoma cells. Cells were treated with 1 μM obatoclax for the indicated time and DEVDase activity was determined. e Flow cytometry analysis of GFP-positive Tsc2+/−Eμ-Myc lymphoma cells as readout for cell survival of cells transduced with shFLuc.1309 or shMcl-1.1334. Cells were transduced once with the indicated constructs and flow cytometry analysis performed 12 h after transduction (t = 0) as well as 15 h later (t = 15). Error bars indicate SEM (n = 3)

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