Abstract
Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemotherapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c in the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Biomarkers
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Biomarkers, Tumor
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Chick Embryo
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Cysteine Proteinase Inhibitors / pharmacology
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Cytochrome c Group / blood
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Cytochrome c Group / metabolism*
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Cytosol / enzymology
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Dactinomycin / pharmacology
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Enzyme Inhibitors / pharmacology
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Extracellular Space / enzymology
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Female
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Hematologic Neoplasms / enzymology
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Humans
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Hydrogen Peroxide / pharmacology
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Jurkat Cells / drug effects
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Jurkat Cells / enzymology
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L Cells / drug effects
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L Cells / enzymology
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L-Lactate Dehydrogenase / analysis
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Male
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Mice
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Middle Aged
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Mitochondria / enzymology*
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Necrosis
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Neoplasm Proteins / blood
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Protein Transport
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Staurosporine / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Amino Acid Chloromethyl Ketones
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Biomarkers
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Biomarkers, Tumor
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Cysteine Proteinase Inhibitors
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Cytochrome c Group
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Enzyme Inhibitors
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Neoplasm Proteins
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Nucleic Acid Synthesis Inhibitors
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Tumor Necrosis Factor-alpha
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Dactinomycin
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Hydrogen Peroxide
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L-Lactate Dehydrogenase
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Staurosporine