Induction and mechanism of apoptotic cell death by propofol in HL-60 cells.
BACKGROUND
Apoptosis (programmed cell death) occurs in various physiological and pathological conditions, exhibits a characteristic mechanism of intracellular sequential reaction and may be involved in determining clinical outcome. The antioxidant activity of propofol (2,6-diisopropylphenol) together with the stimulating effect of protein kinase C suggests that propofol might have the potential to modulate apoptosis. Thus, it is of both clinical interest and biomedical importance to investigate and clarify the effect and mechanism of propofol upon the intracellular reactions underlying apoptotic cell death.


METHODS
The effect of propofol on apoptosis was investigated using cultured human promyelocytic leukemia HL-60 cells. This well-characterized cell line is useful for the study of apoptosis because the various biochemical steps occurring during apoptosis have been well documented.


RESULTS
Treatment of HL-60 cells with propofol resulted in growth inhibition with the formation of apoptotic bodies in a concentration-dependent manner. DNA fragmentation and ladder formation was also observed in a concentration-dependent manner. Propofol treatment resulted in activation of caspase-3, -6, -8 and -9, thereby suggesting that cell surface death receptor activation of the caspase cascade mediates propofol-induced apoptosis with consequent formation of the cleaved product of Bid (a pro-apoptotic Bcl-2 family member protein) and activation of the mitochondrial pathway with cytosolic release of cytochrome c.


CONCLUSIONS
Propofol may induce apoptosis, which is dependent on the mechanism that activates both the cell surface death receptor pathway and the mitochondrial pathway.
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D018686:Anesthetics, Intravenous; D000975:Antioxidants; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D003574:Cytochrome c Group; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; D015742:Propofol