Killing efficacy of a new silicon phthalocyanine in human melanoma cells treated with photodynamic therapy by early activation of mitochondrion‐mediated apoptosis
2004; Wiley; Volume: 13; Issue: 1 Linguagem: Inglês
10.1111/j.0906-6705.2004.00147.x
ISSN1600-0625
AutoresJ Barge, Richard A. Decréau, Michel Julliard, Jean‐Claude Hubaud, Anne‐Sophie Sabatier, Jean‐Jacques Grob, Patrick Verrando,
Tópico(s)Porphyrin and Phthalocyanine Chemistry
ResumoAbstract: Photodynamic therapy (PDT) is a promising therapeutic modality that utilizes a combination of a photosensitizer and visible light for the destruction of diseased tissues. Using human‐pigmented melanoma cells, we examined the photokilling efficacy of new silicon‐phthalocyanines (SiPc) that bore bulky axial substituents. The bis(cholesteryloxy) derivate (Chol‐O‐SiPc) displayed the best in vitro photokilling efficacy (LD 50 = 6–8 × 10 −9 M) and was seven to nine times more potent than chloro‐aluminium Pc (ClAlPc), a known photosensitizer used as a reference. Although Chol‐O‐SiPc was half as potent as ClAlPc for promoting photo‐oxidative membrane damage in a cell‐free assay, early events of mitochondrion‐mediated apoptosis upon PDT were triggered much faster, as demonstrated by kinetics studies examining cells with permeabilized mitochondrial membranes, cytochrome c release and caspase‐9 activation. Inhibition of caspase‐9 activity by a substrate analogue argued for its central role in the proapoptotic events leading to cell death by Chol‐O‐SiPc PDT. In addition, immunoblots showed that Bcl‐2 antiapoptotic oncoprotein was not a primary target of Chol‐O‐SiPc in M3Dau cells treated with PDT. Conclusively, Chol‐O‐SiPc is a useful new photosensitizer with the property of triggering cell apoptosis mediated by mitochondria.
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