Hypericin-induced photosensitization of HeLa cells leads to apoptosis or necrosis - Involvement of cytochrome c and procaspase-3 activation in the mechanism of apoptosis

Here we report that photoactivated hypericin can induce either apoptosis or necrosis in HeLa cells, Under apoptotic conditions the cleavage of poly(AD P-ribose) polymerase (PARP) into the 85-kDa product is blocked by the caspa se 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-induc ed necrosis, Conversely, HeLa cells overexpressing the viral cytokine respo nse modifier A (CrmA), which inhibits caspase-1 and -8, still undergo hyper icin-induced apoptosis and necrosis, Evidence is provided for the release o f mitochondrial cytochrome c in the cytosol and for procaspase-3 activation in the hypericin-induced cell killing, (C) 1998 Federation of European Bio chemical Societies.