A) RPMI-8226vr10 cells were treated with equimolar doses of either of the HDACi (1 μM panobinostat and vorinostat) or proteasome inhibitors (10 nM marizomib and bortezomib) alone and in combination for 24 hours, then stained with PI for analysis of DNA fragmentation (**p < 0.01). B) RPMI-8226vr10 cells were pretreated with a specific caspase-8 inhibitor (IETD-fmk) 30 minutes, followed by treatment with panobinostat, marizomib, and bortezomib alone and in combination for 24 hours. Cells were stained with PI and analyzed for DNA fragmentation (*p < 0.05; **p < 0.01). C) After 12 hours of treatment with the drug combinations used in Fig. 6 A–B, RPMI-8226vr10 cell lysates were probed for caspase-8 cleavage. D–E) RPMI-8226vr10 cells were treated for 12 hours (D) or 24 hours (E) with the 1 μM panobinostat, 1 μM vorinostat, 10 nM bortezomib, or 10 nM marizomib alone and in combination. Lysates were probed for the proteasome subunit β5.