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

 Mi-Ra Kim  ;  Jeong-Yim Lee  ;  Moon-Taek Park  ;  Yong-Jin Chun  ;  Young-Joo Jang  ;  Chang-Mo Kang  ;  Hye Sun Kim  ;  Chul-Koo Cho  ;  Yun-Sil Lee  ;  Hee-Young Jeong  ;  Su-Jae Lee 
 FEBS LETTERS, Vol.505(1) : 179-184, 2001 
Journal Title
Issue Date
Apoptosis/drug effects ; Apoptosis/radiation effects ; Apoptosis Regulatory Proteins ; BH3 Interacting Domain Death Agonist Protein ; Carrier Proteins/metabolism ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspases/drug effects ; Caspases/metabolism ; Caspases/radiation effects ; Cell Death/drug effects ; Clone Cells ; Drug Resistance, Neoplasm* ; Humans ; Jurkat Cells ; Membrane Glycoproteins/pharmacology* ; Proto-Oncogene Proteins/drug effects ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins/radiation effects ; Proto-Oncogene Proteins c-bcl-2/drug effects ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-bcl-2/radiation effects ; Radiation, Ionizing* ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha/pharmacology* ; bcl-2-Associated X Protein
Tumor necrosis factor-related apoptosis-inducing ligand resistance ; Ionizing radiation ; Synergistic cell killing ; TRAIL receptor-independent
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 γ-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 γ-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.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yun Sil(이윤실)
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