Fig. 5: Combined sertraline and chloroquine treatment efficacy relies on the blocking of nucleotide synthesis and the impairment of mitochondrial function.
A Mass spectrometry analysis of the cellular metabolome in response to treatment modalities in U118-MG, GA-MG, LN-18 and GL261 cells. Sertraline is indicated in red, chloroquine treatment in blue and the combination therapy in green, indicated as relative metabolite fold changes (FC) compared to DMSO treated GBM cells. A one-way ANOVA test with Fisher’s Least Significant Difference (LSD) test has been performed. B TMRM mitochondrial staining of 1919 isogenic models. Graphs represent the intensity of TMRM staining corrected by the area in µm3. One-way ANOVA with Dunnett’s multiple comparisons test has been performed. C TMRM intensity/µm3 in 1919 GBM isogenic models treated with DMSO, sertraline, chloroquine, and combination treatment in n = 3 independent experiments and n ≥ 8 pictures per condition in each experiment. One-way ANOVA with Tukey’s multiple comparison test has been performed comparing GFP Ctrl, PSPHamp and PSPHV116I for each treatment group. D Representative images of TMRM staining in 1919 GBM isogenic models upon different treatments using Fire lookup table in Image J. Statistical significance p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****).
