ReferenceID 376
Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK
Cancer Lett
Programmed necrosis is established as a new form of programmed cell death and is emerging as a new strategy of treatment for cancers. Pristimerin is a natural chemical with anti-tumor effect despite the fact that its me
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- Reference Id
- 376
- Evidence Id
- 16966
- Core Evidence Id
- 16966
- Source Reference Id
- 726
- Herb2 Reference Id
- HBREF001255
- Subject Paper Key
- HBIN040737_26854718
- Pubmed Id
- 26854718
- Doi
- 10.1016/j.canlet.2016.01.055
- Paper Title
- Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK
- Paper Abstract
- Programmed necrosis is established as a new form of programmed cell death and is emerging as a new strategy of treatment for cancers. Pristimerin is a natural chemical with anti-tumor effect despite the fact that its mechanism remains poorly understood. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the effect of pristimerin on glioma and its underlying mechanism. We found that pristimerin inhibited the viabilities of glioma cells in vitro and the growth of xenograft gliomas in vivo, which was accompanied by upregulation of JNK and phosphor-JNK, nuclear accumulation of AIF, and elevation in the ratio of Bax/Bcl-2. In vitro studies showed that pristimerin induced necrosis in glioma cells, as well as mitochondrial depolarization, overproduction of ROS and reduction of GSH. Ablation of AIF level with SiRNA mitigated pristimerin-induced nuclear accumulation of AIF and prevented necrosis in glioma cells. Moreover, pharmacological inhibition of JNK with SP600125 or knockdown of its level with SiRNA reversed mitochondrial depolarization attenuated the elevation of Bax/Bcl-2 and suppressed nuclear accumulation of AIF. Further, inhibition of ROS with NAC not only rescued glioma cell necrosis but also suppressed JNK activation, mitigated Bax/Bcl-2 ratio, maintained mitochondrial membrane potential, and inhibited AIF translocation into nucleus. Therefore, we demonstrated first in this study that pristimerin triggered AIF-dependent necroptosis in glioma cells via induction of mitochondrial dysfunction by activation of JNK through overproduction of ROS. These results suggest that pristimerin has potential therapeutic effects on glioma.
- Journal
- Cancer Lett
- Publish Year
- 2016
- Experiment Subject
- glioma cell lines and mice model of xenograft glioma
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK
- Bilingual Status
- semi_complete