1. 14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death
- Author
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Chang-Woo Lee, Han Yk, Park Gy, Lee Cg, Kim Sd, Jo Ws, Yang K, Kim Js, Chun Sh, Jeong Dh, and Han Jy
- Subjects
Cancer Research ,Programmed cell death ,Cell Survival ,medicine.medical_treatment ,Mitosis ,Apoptosis ,Cell Growth Processes ,Biology ,Transfection ,Radiation Tolerance ,Microtubule ,Cell Line, Tumor ,Radioresistance ,medicine ,Humans ,RNA, Small Interfering ,Molecular Biology ,Mitotic catastrophe ,Cell Death ,Brain Neoplasms ,Cell Cycle ,Cell biology ,Radiation therapy ,14-3-3 Proteins ,Cell culture ,Molecular Medicine ,Glioblastoma ,HeLa Cells - Abstract
14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.
- Published
- 2014