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学科主题临床医学
Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis
Zhao, H1; Cai, Y1; Santi, S1; Lafrenie, R1; Lee, H1
刊名RADIATION RESEARCH
2005-09-01
164期:3页:250-257
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biology ; Biophysics ; Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]Life Sciences & Biomedicine - Other Topics ; Biophysics ; Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]RADIATION-INDUCED APOPTOSIS ; CERAMIDE-INDUCED APOPTOSIS ; STRESS-INDUCED APOPTOSIS ; BREAST-CANCER CELLS ; CATHEPSIN-D ; ASCITES HEPATOMA ; DOWN-REGULATION ; GROWTH-STATE ; EXOCYTOSIS ; GENERATION
英文摘要

The anti-malarial drug chloroquine (CQ) is also thought to be a potential radiation sensitizer. To gain a better understanding of how the lysomotropic CQ can potentiate the effects of ionizing radiation, we investigated the effects of CQ on lysosomal and mitochondrial membrane stability, the subcellular localization of ceramide, plasma membrane permeability, and the mode of cell death in response to irradiation. We found that CQ accumulated in the lysosomes and thus lysosomal volumes increased. As a result, both the lysosomal and plasma membranes were destabilized. After 7 Gy irradiation, most ceramide was associated with the lysosomes in the cells treated with CQ but not in the CQ-untreated control. The elevated levels of ceramide in the lysosomes of the CQ-treated cells appeared to further destabilize the lysosomal and plasma membranes of the cell. Both CQ-treated and -untreated cells had approximately the same rate of cell death by apoptosis after 7 Gy irradiation (P > 0.05, ns). However, in contrast to the CQ-untreated control, the CQ-treated cells underwent massive cell death by necrosis at 24-48 h after irradiation (P < 0.05). Taken together, our data support the idea that the increase in cytotoxic effects by the combination of CQ and radiation is due to radiation-mediated apoptosis and CQ-mediated necrosis. (c) 2005 by Radiation Research Society.

语种英语
WOS记录号WOS:000231551500004
引用统计
被引频次:42[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52662
专题北京大学临床肿瘤学院_肿瘤放疗科
作者单位1.NE Ontario Reg Canc Ctr, Dept Res, Sudbury, ON P3E 5J1, Canada
2.Peking Univ, Sch Oncol, Dept Radiat Oncol, Beijing Canc Hosp, Beijing 10036, Peoples R China
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GB/T 7714
Zhao, H,Cai, Y,Santi, S,et al. Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis[J]. RADIATION RESEARCH,2005,164(3):250-257.
APA Zhao, H,Cai, Y,Santi, S,Lafrenie, R,&Lee, H.(2005).Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis.RADIATION RESEARCH,164(3),250-257.
MLA Zhao, H,et al."Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis".RADIATION RESEARCH 164.3(2005):250-257.
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