Bcl-2 resistant mitochondrial toxicity mediated by the isoquinoline carboxamide PK11195 involves de novo generation of reactive oxygen species
2001
PK11195 and Mitochondrial Toxicity in Cancer Cells
publication
Author Information
Author(s): Fennell D A, Corbo M, Pallaska A, Cotter F E
Primary Institution: St Bartholomew's & The Royal London School of Medicine
Hypothesis
Does the PBR ligand PK11195 induce cytotoxicity through the generation of reactive oxygen species in cancer cells?
Conclusion
PK11195 induces cytotoxicity in HL60 human leukaemia cells by generating oxidative stress, which is resistant to Bcl-2.
Supporting Evidence
- PK11195 induced a collapse of the inner mitochondrial membrane potential in HL60 cells.
- Mitochondrial swelling was observed in HL60 cells but not in SUDHL4 cells.
- The production of hydrogen peroxide was induced by PK11195 and was not inhibited by Bcl-2 transfection.
Takeaway
PK11195 can make cancer cells sick by creating harmful substances, even if the cells have a protective protein called Bcl-2.
Methodology
The study investigated the cytotoxic effects of PK11195 on HL60 human leukaemia cells and SUDHL4 lymphoma cells, measuring mitochondrial membrane potential and reactive oxygen species production.
Digital Object Identifier (DOI)
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