The dual role of FSP1 in programmed cell death: resisting ferroptosis in the cell membrane and promoting necroptosis in the nucleus of THP-1 cells
View abstract on PubMed
Summary
This summary is machine-generated.Inhibition of myristoylation switches ferroptosis and necroptosis in acute monocytic leukemia (AML-M5) cells. This finding reveals FSP1-mediated cell death as a potential therapeutic strategy for AML-M5.
Area Of Science
- Cell Death Mechanisms
- Oncology
- Molecular Biology
Background
- Acute monocytic leukemia (AML-M5) presents a significant clinical challenge with high morbidity and poor prognosis.
- Programmed cell death (PCD) is crucial in AML-M5 treatment, yet the interplay between ferroptosis and necroptosis remains poorly understood.
Purpose Of The Study
- To investigate the roles and relationship between ferroptosis and necroptosis in AML-M5.
- To explore the potential of targeting these cell death pathways for therapeutic intervention.
Main Methods
- THP-1 cells were treated with erastin and the myristoylation inhibitor IMP-366.
- Ferroptosis and necroptosis levels were assessed using CCK-8, western blot, qPCR, and electron microscopy.
- Reactive oxygen species (ROS), lipid ROS, and glutathione levels were quantified; FSP1 localization was analyzed.
Main Results
- IMP-366 treatment induced ferroptosis (lipid peroxidation, GSH depletion, mitochondrial shrinkage) by inhibiting FSP1 localization.
- Simultaneously, IMP-366 triggered necroptosis (increased p-RIPK1/p-MLKL, decreased caspase-8) with characteristic morphological changes.
- Ferrostatin-1 reversed necroptosis, indicating a ferroptosis-dependent mechanism.
Conclusions
- Inhibition of myristoylation by IMP-366 effectively switches cell fate towards ferroptosis and ferroptosis-dependent necroptosis in AML-M5 cells.
- FSP1-mediated ferroptosis and necroptosis represent alternative PCD mechanisms in THP-1 cells.
- These findings offer potential therapeutic strategies and targets for treating AML-M5.
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