Ectopic overexpression of each of these antiapoptotic proteins can block this apoptotic signaling cascade, but almost certainly through different mechanisms: sequestration angiogenic activity of Bim, sequestration of both Bim and Bak, and sequestration of Bak. Due to its low binding affinity for Mcl 1, high concentrations of ABT 737 are unable to promote SBHA lethality in Mcl 1 ectopically overexpressing cells. 11A. Moreover, ABT 737, used only at that high concentration, strikingly reduced both basal and SBHA caused Bim/Bcl 2 binding in cells ectopically overexpressing Bcl 2, possibly since the greater concentration of ABT 737 surely could counteract the effects of overexpressed Bcl 2 in a stoichiometric manner. Similar phenomena were observed in Bcl xL overexpressing cells. Apparently, although ectopic Bcl xL overexpression also resulted in a definite increase in the binding of Bak to Bcl xL, high concentrations of ABT 737 substantially homeless Bak from overexpressed Bcl xL, in line with previous results indicating that ABT 737 upsets the Bcl xL/Bak association. Such results raise the likelihood to Mitochondrion that ectopic over-expression of Bcl xL opposes cell death by binding to and neutralizing equally Bim and Bak and that the latter activities are also reversible by growing ABT 737 concentrations. They could also explain the discordance between the disassociation of the practically complete blockade of Bak activation and Bcl xL/Bim by ABT 737 in Bcl xL overexpressing cells coexposed to SBHA and lower concentrations of ABT 737. Finally, in striking contrast to these findings, a high concentration of ABT 737 did not block binding of Mcl 1 to Bim in U937 cells ectopically overexpressing Mcl 1, actually, Bim/Mcl 1 binding was if any such thing somewhat increased. Somewhat, Bicalutamide molecular weight ectopic overexpression of Mcl 1 resulted in a definite escalation in binding of Mcl 1 to Bak, that was not suffering from ABT 737, presumably because this agent does not target Mcl 1. Consistent with these effects, the high concentration of ABT 737 induced activation and Bak and Bax by itself, and this function was significantly enhanced by coadministration of SBHA in cells overexpressing Bcl 2 or Bcl xL, but not in these ectopically overexpressing Mcl 1. Together, these findings are in keeping with the idea that ectopic overexpression of these antiapoptotic proteins acts to stop cell death induced from the SBHA/ABT 737 regimen via neutralization of Bim, neutralization of both Bim and Bak, or neutralization of Bak, respectively. In addition they argue that interference with only the first two of these events is involved in the connection between SBHA and ABT 737. Cell fate is decided by the balance between prodeath and prosurvival indicators, that are controlled precisely by a complicated network of proteins. One possible explanation for this phenomenon might be that ABT 737, which only objectives Bcl xL and Bcl 2, however not Mcl 1, thereby releases Bim from complexes with Bcl 2 and Bcl xL.