Hypericin‐induced photosensitization of HeLa cells leads to apoptosis or necrosis

FEBS Letters

Merlevede, Wilfried⁴  Vandenheede, Jackie R⁴  de Witte, Peter³  Vandenabeele, Peter²  Agostinis, Patrizia⁴  Assefa, Zerihun⁴  Vantieghem, Annelies⁴  Courtois, Stephane¹  Declercq, Wim² 

[1] Department of Dermatology, Faculty of Medicine, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium;Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology (VIB), University of Ghent (RUG), Ledeganckstraat 35, B-9000 Ghent, Belgium;Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmacy, KU Leuven, Van Evenstraat 4, B-3000 Leuven, Belgium;Division of Biochemistry, Faculty of Medicine, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium

关键词: Photodynamic therapy;    Hypericin;    Apoptosis;    Necrosis;    Caspase;    Cytochrome c;    PDT;    photodynamic therapy;    z-VAD-fmk;    benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone;    z-DEVD-fmk;    benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone;    CrmA;    cytokine response modifier A;    PARP;    poly(ADP-ribose) polymerase;    TNF;    tumor necrosis factor-α;    PVDF;    polyvinylidene difluoride;    PBS;    phosphate-buffered saline;    Hyg;    hygromycin;   

DOI  :  10.1016/S0014-5793(98)01416-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown