benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and hypericin

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.

Topics: Amino Acid Chloromethyl Ketones; Anthracenes; Apoptosis; Caspase 3; Caspase Inhibitors; Caspases; Cell Nucleus; Cell Size; Cell Survival; Cysteine Proteinase Inhibitors; Cytochrome c Group; Cytosol; DNA Fragmentation; Enzyme Activation; Enzyme Precursors; HeLa Cells; Humans; Light; Necrosis; Oligopeptides; Perylene; Photosensitizing Agents; Poly(ADP-ribose) Polymerases; Serpins; Viral Proteins