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Ionizing radiation can overcome resistance to TRAIL in TRAIL-resistant cancer cells.

Authors
Kim, MR; Lee, JY; Park, MT; Chun, YJ; Jang, YJ; Kang, CM; Kim, HS; Cho, CK; Lee, YS; Jeong, HY; Lee, SJ
Citation
FEBS letters, 505(1):179-184, 2001
Journal Title
FEBS letters
ISSN
0014-57931873-3468
Abstract
Although the majority of cancer cells are killed by TRAIL (tumor necrosis factor-related apoptosis-inducing ligand treatment), certain types show resistance to it. Ionizing radiation also induces cell death in cancer cells and may share common intracellular pathways with TRAIL leading to apoptosis. In the present study, we examined whether ionizing radiation could overcome TRAIL resistance in the variant Jurkat clones. We first selected TRAIL-resistant or -sensitive Jurkat clones and examined cross-responsiveness of the clones between TRAIL and radiation. Treatment with gamma-radiation induced significant apoptosis in all the clones, indicating that there seemed to be no cross-resistance between TRAIL and radiation. Combined treatment of radiation with TRAIL synergistically enhanced killing of TRAIL-resistant cells, compared to TRAIL or radiation alone. Apoptosis induced by combined treatment of TRAIL and radiation in TRAIL-resistant cells was associated with cleavage of caspase-8 and the proapoptotic Bid protein, resulting in the activation of caspase-9 and caspase-3. No changes in the expressions of TRAIL receptors (DR4 and DR5) and Bcl-2 or Bax were found after treatment. The caspase inhibitor z-VAD-fmk completely counteracted the synergistic cell killing induced by combined treatment of TRAIL and gamma-radiation. These results demonstrated that ionizing radiation in combination with TRAIL could overcome resistance to TRAIL in TRAIL-resistant cells through TRAIL receptor-independent synergistic activation of the cascades of the caspase-8 pathway, suggesting a potential clinical application of combination treatment of TRAIL and ionizing radiation to TRAIL-resistant cancer cells.
MeSH terms
Apoptosis/drug effectsApoptosis/radiation effectsApoptosis Regulatory ProteinsBH3 Interacting Domain Death Agonist ProteinCarrier Proteins/metabolismCaspase 3Caspase 8Caspase 9Caspases/drug effectsCaspases/metabolismCaspases/radiation effectsCell Death/drug effectsClone CellsDrug Resistance, Neoplasm*HumansJurkat CellsMembrane Glycoproteins/pharmacology*Proto-Oncogene Proteins/drug effectsProto-Oncogene Proteins/metabolismProto-Oncogene Proteins/radiation effectsProto-Oncogene Proteins c-bcl-2/drug effectsProto-Oncogene Proteins c-bcl-2/metabolismProto-Oncogene Proteins c-bcl-2/radiation effectsRadiation, Ionizing*TNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alpha/pharmacology*bcl-2-Associated X Protein
PMID
11557065
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
장, 영주
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