Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization

Pyropheophorbide-a methylester (PPME) is a second generation of photosensit izers used in photodynamic therapy (PDT), We demonstrated that PPME photose nsitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c, Preincubation of cell s with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protect ed against apoptosis mediated by PPME photosensitization showing that react ive oxygen species (ROS) are involved as second messengers. On the other ha nd, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (O-1(2)) lifetime only increases necrosis wi thout affecting apoptosis, Since PPME was localized in the endoplasmic reti culum (ER)/Golgi system and lysosomes, other messengers than ROS were teste d such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c releas e from mitochondria, On the other hand, we demonstrated that the transducti on pathways leading to NF-kappaB activation and apoptosis were clearly inde pendent although NF-kappaB was shown to counteract apoptosis mediated by PP ME photosensitization.