Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels

Figure 9

Overexpression of HO-1 protects from oxidative stress. U87 cells were pretreated with 25 μM cobalt protoporphyrin (CoPP) for one hour before treatment with DMSO, 0.5 μM lapatinib (Lapa), 10 μM siramesine (Sira), or the combination of lapatinib+siramesine (L + S) for 24 hours. (a) Reactive oxygen species production was measured by DHE staining. Cells were stained with DHE (10 μM) after treatment, and fluorescence signals were measured by flow cytometry. Standard error represents three independent experiments (). represents statistical significance of . (b) Lipid peroxidation was measured with C11BODIPY (1 μM), and after treatment, both red and green C11-BODIPY fluorescence were measured by flow cytometry. The change in the ratio of green to red fluorescence was used to indicate an increase in lipid peroxidation. Standard error represents three independent experiments (). represents statistical significance of .

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