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Cell death induced by peroxidized low-density lipoprotein: endopepsis
E T Fossel1, C L Zanella, J G Fletcher
1Department of Radiology, Beth Israel Hospital, Boston, MA 02215.
Cancer Research
|March 1, 1994
Summary
Peroxidized low-density lipoprotein (p-LDL) selectively kills cancer cells by entering lysosomes. This leads to enzyme leakage, causing self-degradation, a process termed endopepsis.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Peroxidized low-density lipoprotein (p-LDL) exhibits selective cytotoxicity towards malignant cells.
- The uptake mechanisms and cellular effects of p-LDL are not fully understood.
Purpose of the Study:
- To investigate the cellular uptake and intracellular localization of p-LDL.
- To elucidate the mechanism of p-LDL-induced cell death.
Main Methods:
- Cell culture experiments using p-LDL.
- LDL receptor pathway analysis.
- Lysosomal integrity assays.
- Mitochondrial function assessment.
- Brefeldin A treatment.
- Electron microscopy.
Main Results:
- p-LDL is partially internalized via the LDL receptor and accumulates in lysosomes.
- Lysosomal integrity is compromised, leading to early content leakage into the cytosol.
- This leakage precedes mitochondrial dysfunction and is inhibited by Brefeldin A.
- Cell death exhibits features resembling apoptosis but is characterized by internal enzymatic degradation.
Conclusions:
- p-LDL induces a unique form of cell death, termed endopepsis, driven by lysosomal enzyme release.
- Understanding endopepsis may offer novel therapeutic strategies targeting cancer cells.