Research Paper Volume 14, Issue 16 pp 6381—6414

Synergism of BCL-2 family inhibitors facilitates selective elimination of senescent cells


Figure 6. Analysis of the expression levels of the anti-apoptotic proteins in the cell populations resistant to ABT-199, A1331852, and S63845. (A) Immunoblotting analysis of MCL-1, BCL-2, and BCL-XL anti-apoptotic protein levels in proliferating (P) and IR-induced senescent (IR-P RPE) cells after treatment with ABT-199, A1331852, and S63845. (B) The quantitative analysis of immunoblots (presented in A) comparing the fold-change of anti-apoptotic protein levels in treatment-surviving populations between proliferating and senescent cells. Two independent experiments were analyzed. The mean ± SD is shown. All statistical analyses were carried out using the two-tailed Student's t-test; *, P > 0.05; **, P < 0.01; ***, P < 0.001. (C) BCL-2 protein family targets of inhibitors analyzed (upper panel). Schematic representation of the mechanism of synergy among BH3 mimetics and MCL-1 inhibitors (lower panel). (D) Inhibitor combinations arranged according to the effectiveness of the selective senolytic effect.