Fig. 5: Elesclomol sensitivity is induced by oxidative stress levels. | Nature Communications

Fig. 5: Elesclomol sensitivity is induced by oxidative stress levels.

From: Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma

Fig. 5: Elesclomol sensitivity is induced by oxidative stress levels.

a Representative histogram (left) and quantification (right) of DCF-DA fluorescence in TC-32 cells after Elesclomol-treatment (10 nM, pink) compared to DMSO control (gray). Horizontal bars represent means, n = 8 biologically independent experiments. P values determined via two-sided independent one-sample t-test (TC-32 (P ≤ 0.0001), RDES (P ≤ 0.0001). b MitoSOX Red /MitoTracker Green ratio in EwS cells after Elesclomol-treatment (10 nM). Horizontal bars represent means, n = 3 biologically independent experiments. P values determined via two-sided independent one-sample t-test (TC-32 (P = 0.006), RDES (P = 0.025). c Relative DCF-DA fluorescence in EwS cells after antioxidant-treatment (0.01 mM Nac or 0.1 mM Tiron). Horizontal bars represent means (n indicates the number of biologically independent experiments per condition: Nac: TC-32 (n = 4, P = 0.008), RDES (n = 4, P = 0.018), Tiron: TC-32 (n = 3, P = 0.005), RDES (n = 3, P = 0.045)). P values determined via two-sided independent one-sample t-test. d Elesclomol IC50 in EwS cells after pre-treatment with Nac (0.01 mM) or Tiron (0.1 mM). Horizontal bars represent means (n indicates the number of biologically independent experiments per condition: Nac: TC-32 (n = 5, P = 0.032), RDES (n = 5, P = 0.016); Tiron: TC-32 (n = 4, P = 0.029), RDES (n = 4, P = 0.029)). P values determined via two-sided Mann–Whitney test. e Representative histogram of DCF-DA fluorescence (left) and quantification (right) in TC-32/TR/shSOX6_2 cells 96 h after SOX6 knockdown. Horizontal bars represent means, n = 5 biologically independent experiments. P values determined via two-sided independent one-sample t-test (TC-32: shSOX6_2 (P = 0.001), shSOX6_3 (P = 0.005); RDES: shSOX6_2 (P = 0.025), shSOX6_3 (P = 0.001)). f Relative MitoSOX Red/MitoTracker Green ratios in EwS cells 96 h after SOX6 knockdown. Horizontal bars represent means, n = 3 biologically independent experiments. P values determined via two-sided independent one-sample t-test (TC-32: shSOX6_2 (P = 0.008), shSOX6_3 (P = 0.014); RDES: shSOX6_2 (P = 0.038), shSOX6_3 (P = 0.006)). g Relative Elesclomol IC50 in EwS cells after SOX6 knockdown and treatment with H2O2 (30 µmol/l) for 72 h. Horizontal bars represent means (n indicates the number of biologically independent experiments per condition: TC-32: shSOX6_2 (n = 6, P = 0.002) shSOX6_3 (n = 5, P = 0.032); RDES: shSOX6_2 (n = 6, P = 0.041), shSOX6_3 (n = 5; P = 0.008)). P values determined via two-sided Mann–Whitney test. All error bars represent SEM. ****P ≤ 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05. Source data are provided as a Source Data file.

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