Figure 8.
Alternative ways to target Mcl-1 and sensitize cells to ABT-737
A: IL-3 withdrawal triggers Mcl-1 degradation and Bim accumulation in FDC-P1 cells. Lysates prepared from Bcl-2-overexpressing FDC-P1 cells grown for 0–24 h in the absence of its essential growth factor IL-3 were blotted for Mcl-1, Bim or HSP70 (loading control).
B: IL-3 deprivation sensitizes FDC-P1 cells overexpressing Bcl-2 (squares) or Bcl-xL (circles) to ABT-737. Viability was determined for the cells, cultured with (filled symbols) or without (unfilled symbols) IL-3 and exposed to ABT-737 (0–10 μM) for 24 h.
C: The protein synthesis inhibitor cycloheximide (CHX) and the CDK inhibitor Seliciclib both reduce Mcl-1 expression. HeLa cells were treated with 50 μg/mL cycloheximide or 30 μM Seliciclib (R-roscovitine/CYC202) for 12 h and Mcl-1 expression measured by immunoblotting (HSP-70, loading control).
D: HeLa cells were left untreated, treated with 2.5 μM ABT-737, 50 μg/mL cycloheximide or 30 μM Seliciclib (R-roscovitine/CYC202), or combinations of ABT-737 with cycloheximide or Seliciclib, for 14 h. Statistical analyses were performed using two-tailed unpaired Student’s t-test.
Data in B and D represent means ± SD from 3 independent experiments.