Back to Search
Start Over
Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization
- Source :
- Oncogene. 20(30)
- Publication Year :
- 2001
-
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-kappaB activation and apoptosis were clearly independent although NF-kappaB was shown to counteract apoptosis mediated by PPME photosensitization.
- Subjects :
- Cancer Research
Golgi Apparatus
Apoptosis
DNA laddering
Mitochondrion
Endoplasmic Reticulum
Radiation Tolerance
Second Messenger Systems
Antioxidants
Mannans
Tumor Cells, Cultured
Phosphorylation
Caspase
chemistry.chemical_classification
Mannosephosphates
Photosensitizing Agents
biology
Singlet Oxygen
Caspase 3
Cytochrome c
NF-kappa B
Chloroquine
Cell biology
Mitochondria
Gene Expression Regulation, Neoplastic
Biochemistry
Proto-Oncogene Proteins c-bcl-2
Caspases
Second messenger system
Colonic Neoplasms
Oxidation-Reduction
Proline
Photochemistry
Cytochrome c Group
Radiation-Protective Agents
Adenocarcinoma
Ceramides
Thiocarbamates
Genetics
Humans
Deuterium Oxide
Molecular Biology
Reactive oxygen species
Acetylcysteine
Oxygen
Oxidative Stress
chemistry
Microscopy, Fluorescence
biology.protein
Lysosomes
Reactive Oxygen Species
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 20
- Issue :
- 30
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....00d60ae46917d5d43006283f59d64eb6