Oncogene, 2003-11, Vol.22 (50), p.8168-8177
2003
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Details
- Autor(en) / Beteiligte
- Titel
- DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation
- Ist Teil von
- Oncogene, 2003-11, Vol.22 (50), p.8168-8177
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- DNA-damaging reagents may kill tumor cells through the generation of reactive oxygen species (ROS). Cytotoxic reagents may also induce apoptosis of cancer cells in Fas-FADD-dependent manners. In this study, we explored the possible link between these two apparently distinct pathways in T leukemia cell Jurkat. Our results demonstrated that gamma-irradiation, similar to cisplatin, induced apoptosis by triggering Fas aggregation and activating FADD-caspase-8 apoptotic cascade. The absence of caspase-8 or Fas greatly reduced the sensitivity to apoptosis mediated by DNA-damaging agents. In addition, apoptosis induced by cisplatin and gamma-irradiation, but not by Fas, was inhibited by ROS scavengers, including N-acetyl cysteine, MnTBAP, and C60. Importantly, these ROS scavengers effectively prevented the clustering of Fas receptor induced by cisplatin and gamma-irradiation. Our results suggest that cisplatin and gamma-irradiation promote ROS production, which in turn contributes to Fas receptor aggregation and cell death. The novel coupling between ROS and Fas clustering likely plays a significant role in apoptosis triggered by DNA-damaging reagents in Fas-expressing leukemia cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1206979Titel-ID: cdi_proquest_miscellaneous_71339215
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing, Ageing, cell death, Antineoplastic Agents - pharmacology, Apoptosis, Apoptosis - drug effects, Apoptosis - radiation effects, Biological and medical sciences, Carrier Proteins - metabolism, Caspase 8, Caspase 9, Caspases - metabolism, Cell death, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cisplatin, Cisplatin - pharmacology, Cytotoxicity, Deoxyribonucleic acid, DNA, DNA damage, DNA Damage - radiation effects, Drugs, FADD protein, Fas antigen, Fas Ligand Protein, fas Receptor - radiation effects, Fas-Associated Death Domain Protein, Fundamental and applied biological sciences. Psychology, Gamma Rays, Humans, Jurkat Cells, Kinases, Leukemia, Life sciences, Membrane Glycoproteins - metabolism, Mitochondria, Molecular and cellular biology, Molecular biology, Reactive oxygen species, Reactive Oxygen Species - metabolism, Reagents, Tumor cells, γ Radiation