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

Figure 10

Bilirubin protects from cell death. U87 cells were pretreated with 100 nM bilirubin 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) Cell death was quantified by trypan blue exclusion assay using flow cytometry. (b) Lipid peroxidation was measured with C11BODIPY (1 μM), and after 24 hours, 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. (c) Reactive oxygen species production was measured by DHE staining. U87 cells were stained with DHE (10 μM); after 24 hours of treatment, fluorescence signals were measured by flow cytometry. Standard error represents three independent experiments (). represents statistical significance of .

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