Fig. 1: Cabozantinib induces G0/G1 cell-cycle arrest and apoptosis in KIT-mutated t(8;21) AML cells.

A Kasumi-1 and SKNO-1 cells were treated with 0.01% DMSO (control) or various concentrations of cabozantinib for 72 h. MTS assay was performed to obtain the IC₅₀ values of cabozantinib for both cell lines. The IC₅₀ values were calculated using the CalcuSyn software. B Flow cytometric analysis after 24-h cabozantinib represents the proportion of cells at different cell-cycle stages. Histograms are one of the representative results. The data represented the averages ± SD of three independent experiments (n = 3). ***p < 0.001, **p < 0.01, *p < 0.05, compared with DMSO control. C Two G1/S transition regulators, p27 and cyclin E, were measured by western blot analysis. β-actin was loaded as a control. Signal intensity was quantified with ImageJ and normalised to β-actin and DMSO controls. D Flow cytometric analysis after 72-h cabozantinib treatment is presented as dot plots and the bar graphs show the proportion of cells at different apoptotic status. Each column represented the averages ± SD of three independent experiments (n = 3). ***p < 0.001, **p < 0.01, *p < 0.05, compared with DMSO control. E Western blot analysis of PARP cleavage, caspase-3 activation and F apoptosis-related proteins, including BAX, BAK, PUMA, Survivin, MCL-1, and BCL-2, in Kasumi-1 cells following 24-h cabozantinib treatment. G BBC3 and survivin relative mRNA expression were analysed by RT-qPCR analysis following 24-h cabozantinib treatment. Each column represented the averages ± SD of three independent experiments (n = 3). ***p < 0.001, **p < 0.01, *p < 0.05, compared with DMSO control.