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(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.
Vantieghem
A
A
Division of Biochemistry, Faculty of Medicine, KU Leuven, Belgium.
Assefa
Z
Z
Vandenabeele
P
P
Declercq
W
W
Courtois
S
S
Vandenheede
J R
JR
Merlevede
W
W
de Witte
P
P
Agostinis
P
P
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000873:Anthracenes; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D009336:Necrosis; D009842:Oligopeptides / Q000494:pharmacology; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
D000590:Amino Acid Chloromethyl Ketones; D000873:Anthracenes; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D009842:Oligopeptides; D017319:Photosensitizing Agents; D015843:Serpins; D014764:Viral Proteins; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D010569:Perylene; C004965:hypericin; C074641:interleukin-1beta-converting enzyme inhibitor; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases