Abstract
Here we report that photoactivated hypericin can induce either apoptosis or necrosis in HeLa cells. Under apoptotic conditions the cleavage of poly(ADP-ribose) polymerase (PARP) into the 85-kDa product is blocked by the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (z-DEVD-fmk). Both inhibitors protect cells from apoptosis but cannot prevent hypericin-induced necrosis. Conversely, HeLa cells overexpressing the viral cytokine response modifier A (CrmA), which inhibits caspase-1 and -8, still undergo hypericin-induced apoptosis and necrosis. Evidence is provided for the release of mitochondrial cytochrome c in the cytosol and for procaspase-3 activation in the hypericin-induced cell killing.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Anthracenes
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Apoptosis*
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Caspase 3
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Caspase Inhibitors
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Caspases / metabolism*
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Size / drug effects
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Cell Survival / drug effects
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Cysteine Proteinase Inhibitors / genetics
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Cysteine Proteinase Inhibitors / metabolism
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Cysteine Proteinase Inhibitors / pharmacology
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Cytochrome c Group / metabolism*
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Cytosol / metabolism
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DNA Fragmentation / drug effects
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Enzyme Activation
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Enzyme Precursors / metabolism*
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HeLa Cells
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Humans
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Light
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Necrosis*
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Oligopeptides / pharmacology
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Perylene / analogs & derivatives*
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Perylene / pharmacology
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Photosensitizing Agents / pharmacology*
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Poly(ADP-ribose) Polymerases / metabolism
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Serpins / genetics
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Serpins / metabolism
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Viral Proteins*
Substances
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Amino Acid Chloromethyl Ketones
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Anthracenes
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Caspase Inhibitors
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Cysteine Proteinase Inhibitors
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Cytochrome c Group
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Enzyme Precursors
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Oligopeptides
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Photosensitizing Agents
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Serpins
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Viral Proteins
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Perylene
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hypericin
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interleukin-1beta-converting enzyme inhibitor
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Poly(ADP-ribose) Polymerases
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CASP3 protein, human
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Caspase 3
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Caspases