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

FEBS Letters

Lee, Su-Jae³  Park, Moon-Taek³  Jang, Young-Joo¹  Lee, Yun-Sil³  Chun, Yong-Jin³  Lee, Jeong-Yim⁴  Cho, Chul-Koo³  Jeong, Hee-Young²  Kang, Chang-Mo³  Kim, Hye Sun⁴  Kim, Mi-Ra³ 

[1] Laboratory of Immunology, Medical Research Institute, Ajou University, Suwon 442-749, South Korea;Department of Microbiology, College of Medicine, Han-Yang University, Seoul 133-791, South Korea;Laboratory of Radiation Effect, Korea Cancer Center Hospital, Gongneung-Dong, Nowon-Ku, Seoul 139-706, South Korea;Department of Biological Sciences, Ajou University, Suwon 442-749, South Korea

关键词: Tumor necrosis factor-related apoptosis-inducing ligand resistance;    Ionizing radiation;    Synergistic cell killing;    TRAIL receptor-independent;    TNF;    tumor necrosis factor;    TRAIL;    TNF-related apoptosis-inducing ligand;    DR;    death receptor;    DcR;    decoy receptor;    PARP;    poly(ADP-ribose) polymerase;    z-VAD-fmk;    benzyloxycarbonyl-Phe-Val-Ala-Asp (Ome)-fluoromethylketone;   

DOI  :  10.1016/S0014-5793(01)02816-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown