Premium
Different Pathways Mediate Cytochrome c Release After Photodynamic Therapy with Hypericin
Author(s) -
Vantieghem Annelies,
Xu Yan,
Declercq Wim,
Vandenabeele Peter,
Denecker Geertrui,
Vandenheede Jackie R.,
Merlevede Wilfried,
De Witte Peter A.,
Agostinis Patrizia
Publication year - 2001
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2001)0740133dpmccr2.0.co2
Subject(s) - hypericin , photodynamic therapy , chemistry , pharmacology , medicine , organic chemistry
In this study we show that overexpression of Bcl‐2 in PC60R1R2 cells reveals a caspase‐dependent mechanism of cytochrome c release following photodynamic therapy (PDT) with hypericin. Bcl‐2 overexpression remarkably delayed cytochrome c release, procaspase‐3 activation and poly(adenosine diphosphate‐ribose)polymerase cleavage during PDT‐induced apoptosis while it did not protect against PDT‐induced necrosis. PDT‐treated cells showed a reduction in the mitochondrial membrane potential which occurred with similar kinetics in PC60R1R2 and PC60R1R2/Bcl‐2 cells, and was affected neither by the permeability transition pore inhibitor cyclosporin A nor by the caspase inhibitor N ‐benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethylketone (zVAD‐fmk). Hypericin‐induced mitochondrial depolarization coincided with cytochrome c release in PC60R1R2 cells while it precedes massive cytochrome c efflux in PC60R1R2/Bcl‐2 cells. Preincubation of PC60R1R2 cells with zVAD‐fmk or cyclosporin A did not prevent the mitochondrial efflux of cytochrome c, and caspase inhibition only partially protected the cells from PDT‐induced apoptosis. In contrast, in PC60R1R2/Bcl‐2 cells cytochrome c release and apoptosis were suppressed by addition of zVAD‐fmk or cyclosporin A. These observations suggest that the progression of the PDT‐induced apoptotic process in Bcl‐2–overexpressing cells involves a caspase‐dependent feed‐forward amplification loop for the release of cytochrome c.