Fig. 8: Targetable ROS-scavenging mechanisms selectively sensitize human breast cancers to multiple mitochondrial complex I inhibitors. | Nature Communications

Fig. 8: Targetable ROS-scavenging mechanisms selectively sensitize human breast cancers to multiple mitochondrial complex I inhibitors.

From: STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer

Fig. 8

a DCFDA geometric mean fluorescence intensity (MFI) for immortalized NMuMG and transformed NMuMG-NeuNT cells treated with PBS or phenformin (500 μM) for 24 h. The data are shown as fold change in MFI compared to NMuMG cells and represent the mean of n = 4 independent experiments (±SEM). Representative histograms are shown. b Viability of cells described in (a) in response to phenformin (500 μM) and/or BSO (100 μM) treatment (upper graph) or phenformin (500 μM) and/or β-lapachone (4 μM) treatment (lower graph) for 48 h. The data are shown as fold change in viability compared to vehicle and is representative of n = 4 (upper graph) or n = 3 independent experiments (lower graph), presented as mean of means ± SEM. c Viability of BT474 and MDA-MB-231 cells treated with IACS-010759 (50 nM) and/or β-lapachone (BT474: 1.0 μM and MDAMB231: 0.5 μM) for 48 h. The data are shown as fold change in viability compared to DMSO, n = 4 independent experiments (mean of means) ± SEM (MDA-MB-231); or of n = 8 technical replicates, over two independent experiments ± SD (BT474). d DCFDA geometric MFI for MDA-MB-231 cells treated with IACS-010759 (50 nM) and/or β-lapachone (0.5 μM) for 24 h. The data are shown as fold change in MFI compared to DMSO and are representative of n = 3 independent experiments ± SEM. e, f Viability of HER2+ PDXs (CRC-132, GCRC2080) in vitro after treatment with phenformin (CRC-132, 100 μM; GCRC2080, 500 μM) alone and with (e) BSO (300 μM) or (f) β-lapachone (0.5 μM), for 48 h. The data are shown as fold change in viability compared to vehicle and is representative of n = 3 independent experiments (mean of means) ± SEM. g, h Viability of basal-like PDXs (GCRC1735, GCRC1915, GCRC1963, and GCRC1986) in vitro after treatment with g phenformin (500 μM) and/or BSO (300 μM) or h phenformin (500 μM) and/or β-lapachone (1 μM) for 48 h. The data are shown as fold change in viability compared to vehicle and are representative of n = 3 independent experiments (mean of means) ± SEM. P values were calculated using a two-way ANOVA with a Tukey’s post hoc test. See also Supplementary Figures 9 and 10.

Back to article page