The combination of LCL161 and LBH589 activates the canonical NF-κB pathway and induces DNA damage in MM cells. (A and B) U266 cells or MM.1S cells were exposed to the indicated concentrations of LBH ± LCL for 16 hours (U266) or 24 hours (MM.1S). Immunoblotting analysis was then performed to monitor levels of cIAP1, cIAP2, γH2A.X, p-p65, and p65. β-actin was assayed to ensure equivalent loading and transfer. All experiments were repeated three times. (C and D) DNA binding of NF-kB (p65 subunit) was determined by using a TransAM assay for NF-κB activity.