Artesunate induces necrotic cell death in schwannoma cells

被引:51
作者
Button, R. W. [1 ,2 ]
Lin, F. [3 ]
Ercolano, E. [1 ,2 ]
Vincent, J. H. [1 ,2 ]
Hu, B. [4 ]
Hanemann, C. O. [1 ,2 ]
Luo, S. [1 ,2 ]
机构
[1] Univ Plymouth, Peninsula Sch Med, Inst Translat & Stratified Med, Plymouth PL6 8BU, Devon, England
[2] Univ Plymouth, Peninsula Sch Dent, Inst Translat & Stratified Med, Plymouth PL6 8BU, Devon, England
[3] Soochow Univ, Sch Pharmaceut Sci, Suzhou 215123, Peoples R China
[4] Univ Plymouth, Peninsula Sch Med, Plymouth PL6 8BU, Devon, England
关键词
PANCREATIC-CANCER CELLS; MIXED LINEAGE KINASE; IN-VIVO; POLY(ADP-RIBOSE) POLYMERASE; ARTEMISININ COMPOUNDS; PROGRAMMED NECROSIS; BREAST-CANCER; UP-REGULATION; CYCLE ARREST; RIP1; KINASE;
D O I
10.1038/cddis.2014.434
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity.
引用
收藏
页码:e1466 / e1466
页数:10
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