Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels
Silencing expression of HO-1 combined with siramesine induces cell death. (a) U87 cells were knockdown in HO-1 expression by siRNA as demonstrated by Western blot; 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 treated with DMSO, 0.5 μM lapatinib (Lapa), 10 μM siramesine (Sira), or the combination of lapatinib+siramesine (L+S). Transfected (HO-1siRNA) and control transfected (Tctrl) U87 cells were treated with DMSO, 0.5 μM lapatinib (HO-1siRNA+L and Tctrl+L, respectively), and 10 μM siramesine (HO-1siRNA+S and Tctrl+S, respectively) 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 .
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