Photodynamic activity of a glucoconjugated silicon(IV) phthalocyanine on human colon adenocarcinoma

Photodynamic therapy (PDT) involves the use of a non-toxic photosensitizer which exhibits killing effect upon activation by light. In the past few years, we have synthesized a number of novel second generation photosensitizers of superior properties, most of them are phthalocyanines. Among them, the glucoconjugated silicon(IV) phthalocyanine, SiPcGlu, shows potent phototoxicity against the human colorectal adenocarcinoma HT29 cells. In the present study, its action mechanism was investigated. The initiation of apoptosis by SiPcGlu-PDT, subsequent to reactive oxygen species production, was shown by the results of TUNEL assay, annexin V & propidium iodide staining and DNA ladder pattern analysis. Confocal microscopy revealed the presence of SiPcGlu in lysosome, mitochondria and endoplasmic reticulum. SiPcGlu-PDT did not cause any damage to the lysosomal membrane; whereas in the mitochondria, it caused membrane depolarization and the release of cytochrome c into the cytosol, which subsequently brought about caspase-3 activation. In the endoplasmic reticulum, the treatment led to Ca2+ release and an increase in the expression level of the chaperone protein GRP78. These observations suggest that SiPcGlu-PDT triggered the apoptotic pathways in both mitochondria and endoplasmic reticulum, but not the lysosome. A preliminary study of the photodynamic activity of SiPcGlu in the in vivo animal model was also carried out. It retarded tumor growth in HT29 tumor-bearing nude mice while causing no apparent toxicity to the animal.