β-Catenin contributes to enzastaurin-induced cell death via induction of c-Jun and p73. (A) After knockdown of β-catenin by siRNA, indicated cell lines were exposed to enzastaurin at increasing concentrations and cell survival was assessed by MTT assay during the last 4 hours of 48-hour cultures (siControl vs siCatenin, P < .001). (B) Knockdown of β-catenin inhibits induction of c-Jun and p73 in MM cells. MM.1S cells were exposed to enzastaurin (5 μΜ, 24 hours) after transient transfection with mock or β-catenin siRNA; immunoblots were probed with indicated antibodies. (C) After knockdown of c-Jun or p73 by siRNA, indicated cell lines were exposed to enzastaurin at increasing concentrations, and cell survival was assessed by MTT assay during the last 4 hours of 48-hour cultures (siControl vs siJun/p73, P < .001). (D) Depletion of c-Jun inhibits induction of p73 but does not change β-catenin accumulation in MM cells. (E) Inhibition of β-catenin accumulation or p73 induction by siRNA rescues MM cells from enzastaurin-induced apoptosis. MM.1S cells were exposed to enzastaurin (5 μΜ, 24 hours) after depletion of β-catenin or p73 by siRNA. Cell lysates were subjected to immunoblotting with indicated antibodies (top), and induction of apoptosis was assessed by DNA fragmentation (bottom).