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

FEBS Lett. 1998 Nov 27;440(1-2):19-24. doi: 10.1016/s0014-5793(98)01416-1.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Anthracenes
  • Apoptosis*
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Size / drug effects
  • Cell Survival / drug effects
  • Cysteine Proteinase Inhibitors / genetics
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytochrome c Group / metabolism*
  • Cytosol / metabolism
  • DNA Fragmentation / drug effects
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • HeLa Cells
  • Humans
  • Light
  • Necrosis*
  • Oligopeptides / pharmacology
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology
  • Photosensitizing Agents / pharmacology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Serpins / genetics
  • Serpins / metabolism
  • Viral Proteins*

Substances

  • Amino Acid Chloromethyl Ketones
  • Anthracenes
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Cytochrome c Group
  • Enzyme Precursors
  • Oligopeptides
  • Photosensitizing Agents
  • Serpins
  • Viral Proteins
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Perylene
  • hypericin
  • interleukin-1beta-converting enzyme inhibitor
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Caspases