Extended Data Fig. 9: Fento-1 induces ferroptosis in CD44high iron-rich cancer cells (Part 2).
From: Activation of lysosomal iron triggers ferroptosis in cancer
a, Viability of cells treated with Fento-1 or standard-of-care chemotherapy for 72 h. Data are mean ± s.e.m. n = 3 independent experiments. b, Viability of PDAC-derived organoids treated with Fento-1 or standard-of-care chemotherapy for 72 h. Data are mean ± s.e.m. IC50-values are indicated. PDAC009T: Oxaliplatin, 5-FU and SN-38 n = 4 independent experiments, Fento-1 n = 2 independent experiments. PDAC003T: Oxaliplatin n = 6 independent experiments, 5-FU and SN38 n = 4 independent experiments, Fento-1 n = 3 independent experiments. PDAC117T: Oxaliplatin, 5-FU and SN-38 n = 7 independent experiments, Fento-1 n = 3 independent experiments. PDAC372T: Oxaliplatin, 5-FU and SN-38 n = 4 independent experiments, Fento-1 n = 3 independent experiments. c, Viability of cells treated with standard-of-care chemotherapy and sublethal doses of Fento-1 (1.5 µM, 72 h). 1-way ANOVA. Data are mean ± s.e.m. n = 3 independent experiments. d, Synergy score of standard-of-care chemotherapy and Fento-1 in human primary PDAC cells. e, Viability of cells treated with Fento-1 (72 h) in naive cells or cells pretreated with Doxo (25 nM) for 30 days, then treated with Fento-1 for 72 h. Data are mean ± s.e.m. n = 5 independent experiments. f, Bright field images of cells treated with Doxo (25 nM, 30 days). Scale bar, 100 μm. Representative of n = 3 independent experiments with similar results. g, CD44 flow cytometry of cells treated with Doxo (25 nM) or Fento-1 (1 µM) for 10 days. Representative of n = 3 independent experiments. h, Western blot of mesenchymal and iron homeostasis markers in cells treated with Doxo (25 nM) for 10 days. Lamin A/C is a sample loading control. Representative of n = 3 independent experiments with similar results. i, Western blot of mesenchymal and iron homeostasis markers in cells treated with Fento-1 (1 µM) for 10 days. γ-tubulin is a sample loading control. Representative of n = 3 independent experiments with similar results. Doxo, doxorubicin.
