Figure 6.

Pevonedistat did not initiate cytotoxic effects through inhibition of NFκB signaling, but through DNA re-replication/damage in AML cells. A. AML cell lines MV4–11 and Molm-13 cells were treated with S, P or S + P for 16 hours and western blot analysis was performed to detect the levels of NEDD8-cullin, IKBα, CDT-1 and γH2A.X (S139). GAPDH was probed as loading control. B. U937 cells were treated with different concentrations of P for 24 or 48 hours. Western blot analysis was performed to detect NFκB pathway markers. C. KG1a NFκB luciferase reporter cells were treated with 400 nM of S, P or S + P for 3, 5, 7, or 18 h. At the end of time point, the luciferase activity was detected. *P < .05, **P < .01 compared to DMSO vehicle control using two-way ANOVA followed by Bonferroni post-tests.