Figure 2.
LCL-161 decreases the expression of several IAPs and induces apoptosis. (A-B) The rituximab-sensitive lymphoma cell line Raji/RL and the rituximab-resistant clone Raji 4RH/RL 4RH were exposed to escalating doses of LCL-161 (0-40 μM, as indicated) for 24 hours prior to protein extraction. LCL-161 decreased the expression of cIAP1, cIAP2, and livin in a dose-dependent manner at 24 hours postexposure. LCL-161 induced PARP cleavage at concentrations of 20 and 40 μM in the resistant Raji 4RH cell line. In RL cells, LCL-161 decreased the expression cIAP1, survivin, and livin in a dose-dependent manner at 24 hours postexposure. LCL-161 induced PARP cleavage at concentrations of 20 and 40 μM in the RL cell line, but not in the RL 4RH cell line. (C) LCL-161 produces a dose-dependent increase in caspase 3/7 activity in the germinal center B-cell DLBCL cell line Karpas 422 at 48 hours.