PK + bortezomib–induced apoptosis is associated with activation of caspase-8 and caspase-3. (A) MM.1S cells were treated with PK (50 μM), bortezomib (2 nM), or PK + bortezomib for 24 hours; cytosolic proteins were separated by 12.5% SDS-PAGE and analyzed by immunoblotting with anti–caspase-8 (top panel) and anti–caspase-3 (bottom panel) Abs. Blots are representative of 3 independent experiments. FL indicates full length; CF, cleaved fragment. (B) PK + bortezomib–induced apoptosis is mediated by both caspase-8, caspase-9 >> caspase-3 pathway. MM.1S cells were treated with PK + bortezomib alone or in the presence of caspase-8 inhibitor, caspase-9 inhibitor, or pan–caspase-3 inhibitor for 24 hours; harvested; and assessed for viability using MTT assays. Results are means ± SDs of 3 independent experiments (P < .005).