Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels
Proteasome inhibition abolish the decrease of HO-1 expression induced by lapatinib-siramesine combination. (a) U87 cells were treated with 5 μM MG132 for 24 hours; then, cells were lysed, Western blot determination of protein ubiquitination using the anti-ubiquitin antibody was performed, and actin was used as a loading control. The image showing protein ubiquitination is representative of three independent experiments (). (b) U87 cells were pretreated with 5 μM MG132 for one hour before treatment with DMSO, 0.5 μM lapatinib (Lapa), 10 μM siramesine (Sira), or the combination of lapatinib+siramesine (L+S). After 24 hours of treatment, cells were lysed, Western blot determination of HO-1 and Nrf2 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 .
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