Fig. 4: AUR potentiates apoptosis induction by VEN and strongly upregulates pro-apoptotic protein NOXA.

A SEM cells were exposed to VEN, AUR and a combination of both drugs for 1, 2 and 4 h, and then mitochondrial ROS levels were detected by MitoSOX assay. The bars represent mean fold change in mean fluorescence intensity (MFI) over untreated control (DMSO) + SD, n = 4. **P < 0.01 by one-way ANOVA with Bonferroni post-hoc test. B SEM cells were treated with VEN, AUR, and both drugs for 16 h and subjected to MultiCaspase assay. Activation of caspases and cell death was determined by staining of the cells with fluorescently-labeled inhibitor of caspases (FLICA) and 7AAD dye and analyzed using Muse Cell Analyzer. The bars show mean values + SD (n = 4). Statistical analysis was performed using a two-way ANOVA test, and the significance for the interaction factor was presented, **P < 0.01. C SEM cells were exposed to indicated concentrations (in nM) of VEN, 0.8 μM AUR and a combination of both drugs for 4, 8, and 24 h. The levels of particular members of BCL-2 family proteins were determined by immunoblotting. The graph shows representative blots of at least two independent experiments. α-tubulin serves as a loading control.