Fig. 4: The SETD8 inhibitor UNC0379, in synergy with the Wee1 inhibitor adavosertib, induces cell death through mitotic catastrophe in glioblastoma cell lines. | Cell Death & Disease

Fig. 4: The SETD8 inhibitor UNC0379, in synergy with the Wee1 inhibitor adavosertib, induces cell death through mitotic catastrophe in glioblastoma cell lines.

From: Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth

Fig. 4

a LN-18 and U251 cells were treated with vehicle (CTRL), 5 μM UNC0379 and 400 nM adavosertib (Adv), alone or in combination, for 48 h. Cell viability was monitored by MTT assay. Statistical analyses were performed by one-way ANOVA, followed by multiple t test and p value was referred to CTRL. All values are given as mean ± standard deviation of at least three replicates. ***p < 0.001. b Cell cycle distribution of cells, treated as in (a), was monitored by FACS analysis. Percentage of cells in G1/S and G2/M is indicated. Statistical analyses were performed using one-way ANOVA, followed by multiple t-test. In panel, we indicated one-way ANOVA p value. p value was referred to CTRL G1/S and G2/M. ***p < 0.001; *p < 0.05. c Death of cells, treated as in (a), was assessed detecting caspase activity. To inhibit caspase activity, cells were also incubated with z-VAD-FMK (+ z-VAD) from the time of UNC0379+adavosertib addition. Statistical analyses were performed by one-way ANOVA, followed by multiple t test and p value was referred to CTRL. All values are given as mean ± standard deviation of at least three replicates. *** p < 0.001; ** p < 0.001. d Cells, treated as in (a), were lysed and death was assessed monitoring cleavage of PARP and caspase 3 proteins by western blot. Protein levels were normalized by β-actin probing.

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