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

Jean Yves Matroule, Chris M. Carthy, David J. Granville, Olivier Jolois, David W C Hunt, Jacques Piette

Research output: Contribution to journalArticlepeer-review

Abstract

Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization 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 cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-κ-B activation and apoptosis were clearly independent although NF-κB was shown to counteract apoptosis mediated by PPME photosensitization.
Original languageEnglish
Pages (from-to)4070-4084
Number of pages15
JournalOncogene
Volume20
Issue number30
DOIs
Publication statusPublished - 5 Jul 2001
Externally publishedYes

Keywords

  • Apoptosis

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