Fig. 3: AURKA inhibition facilitates oxidative energy metabolism. | Nature Communications

Fig. 3: AURKA inhibition facilitates oxidative energy metabolism.

From: Aurora kinase A inhibition reverses the Warburg effect and elicits unique metabolic vulnerabilities in glioblastoma

Fig. 3

a GBM22 cells were treated with DMSO or alisertib and analyzed for oxygen consumption rate (OCR) on a Seahorse XFe24 device. OM: oligomycin, R/A rotenone/antimycin. The graph (right panel) shows the OCR levels (n = 5 in DMSO, Ali 1 μM, Ali 5 μM; n = 4 in Ali 10 μM independent samples) (Ali 1 μM: *p = 0.0303, Ali 5 μM: **p = 0.0074, Ali 10 μM: *p = 0.0254). For b, c Seahorse mitochondrial stress assay of parental or chronically alisertib treated GBM22 and SF188 cells. The graph (right panel) shows the mitochondrial OCR levels (n = 3 in SF188 vs SF188AR, n = 5 in GBM22 vs GBM22AR independent samples) (**p = 0.0014, ***p = 0.0001). d SF188 cells were transduced with sgRNA against AURKA and were analyzed for the oxygen consumption rate (OCR) on a Seahorse XFe24 device. The graph (right panel) shows the mitochondrial OCR level (n = 5 independent samples) (**p = 0.0016). e Electron microscopy of parental or chronically alisertib treated U87 cells. Scale bar: 2 µm. Higher magnification images are shown in the lower panel. Scale bar: 500 nm. The white dotted square shows the enlarged region of mitochondria in the lower panel. The red arrow highlights the mitochondrial morphology. f GBM22 cells were treated with DMSO or alisertib for 24 h, labeled with either CellRox or Mitotracker dye, and analyzed by flow cytometry (n = 2 independent samples). g GBM22 cells were treated with 1 µM alisertib, 2 µM GTPP, or the combination of both for 24 h and analyzed for oxygen consumption rate (OCR) on a Seahorse XFe24 device. The graph (below panel) shows the mitochondrial OCR level (n = 3 in DMSO and Combination, n = 4 in Ali 1 μM and GTPP 2 μM independent samples) (***p = 0.0001, ****p < 0.0001). For h, i SF188 and GBM22 cells were treated with alisertib, GTPP, or the combination of both for 72 h. Thereafter, cellular viability was measured, and statistical analysis was performed. Isobolograms are shown. The graphs in (i) show the quantification (n = 4 independent samples) (****p < 0.0001). For j, k SF188 and GBM22 cells were treated with alisertib, oligomycin, or the combination of both for 72 h. Thereafter, cellular viability was determined and statistical analysis was performed. Isobolograms are shown. The quantification is shown in (k) (n = 4 independent samples) (**p = 0.0015, ****p < 0.0001). Data are shown as mean ± SD in (a−d, g, i, k). Source data are provided as a Source Data file.

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