Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels
Overexpression of HO-1 inhibits lapatinib and siramesine cell death. (a) U87 cells were treated with 25 μM cobalt protoporphyrin (CoPP) for 24 hours; then, cells were lysed, Western blot determination of HO-1 was performed, and actin was used as a loading control. Densitometry was calculated using ImageJ. Standard error represents three independent experiments (). represents statistical significance of . (b) U87 cells were pretreated with 25 μM 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. Cell death was quantified by trypan blue exclusion assay using flow cytometry. Standard error represents three independent experiments (). represents statistical significance of ; ns: not significant.
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