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

Figure 5

Lapatinib and siramesine combination increases ROS and lipid peroxidation. A549 and U87 cells were treated with DMSO (D), 0.5 μM lapatinib (L), 10 μM siramesine (S), or the combination of lapatinib+siramesine (L+S). (a) Reactive oxygen species production was measured by DHE staining. A549 and 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 . (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. Standard error represents three independent experiments (). represents statistical significance of .

(a)

(b)