A Ploidy Increase Promotes Sensitivity of Glioma Stem Cells to Aurora Kinases Inhibition
Danusertib induces a cytokinesis failure and delayed mitotic exit in sensitive and resistant GSCs, independently of the T53 mutational status. (a) Representative images of dividing cells (indicated by white arrows) detected by means of live cell imaging analysis (see also Supplementary Videos S1, S2, S3, and S4) show that GSCs were able to enter into mitosis after Danusertib exposure but not to divide through cytokinesis. (b) Quantitative data concerning the cells fate after treatment confirm that Danusertib 500 nM inhibited cytokinesis in sensitive and resistant GSCs. The other parameters evaluated, such as the cell death, did not show any relevant variations. Results represent the means from three different experiments. At least 100 cells were analyzed. For statistical analysis, see Supplementary Table S3. (c) Danusertib induced a significant increase in the mitotic length, determined analyzing the live cell movie by means of Image J. Results represent the means from three different experiments. At least 100 cells were analyzed. t-test was performed on raw data: p<0,001. (d) Electropherograms of TP53 mutational hot spot regions highlighted that all the GSC lines carried missense mutations in the DNA-binding region of the protein, except for GliNS2 line, which was not affected by any mutation.
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