Figure 7.

BPM31510 decreases cell viability in patient-derived organoids (PDO) derived from pancreatic tumours, alters G3PDH and Complex II-dependent respiration, and promotes substrate-specific reactive oxygen species (ROS) production. (a) Haematoxylin and eosin-stained PDOs (left panel). PDO viability after treatment with BPM31510 (right panel). PDOs were untreated or treated with either DMSO or a toxic mix of cyclohexane (50 µg/mL) and puromycin (2 µg/mL), gemcitabine (1 or 10 µM), 5-FU (1 or 10 µM), or BPM31510 (100–10,000 µM) for 72 h, and cell viability was assessed using a CytoTOX Glo cytotoxicity assay. The data represent the means ± SEM of three biological replicates. (b) BPM31510 decreases PDO size after 72 h of treatment. Representative images of PDO after 3 and 7 days of treatment with BPM31510 (left). The boxplots represent the distribution of PDO size following treatment (right). (c) Mitochondrial H₂O₂ generation during succinate-driven (left) and G3PDH-driven (right) respiration in PDOs after BPM31510 treatment. The data represent the means ± SEM of three independent experiments. All data were analysed by one-way ANOVA followed by Dunnett’s or Tukey’s post hoc test; *p < 0.05, ***p < 0.01, ****p < 0.001 compared to the untreated control group.