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Abstract Title:Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP轴。
摘要来源:
细胞增殖。 2020 Jan; 53(1):E12706。 EPUB 2019 10月23日。PMID: 31642559 31642559 Xiangjin Zheng, Jinhua Wang, Guanhua Du
Article Affiliation:Qin Tang
Abstract:OBJECTIVE: Withaferin A (WA) is a bioactive compound with a remarkable anti-cancer effect derived from Withania somnifera, commonly known as Ashwagandha。但是,胶质母细胞瘤多形(GBM)中WA的抗癌机制仍不清楚。
材料和方法: 细胞活力测定和异种移植的裸鼠用于评估WA的作用以及流式细胞仪以检测GBM的凋亡和细胞周期。 RNA-seq analysis, Western blotting, immunofluorescence staining, qRT-PCR and siRNA gene silencing were carried out to determine the signalling pathways affected by WA.
RESULTS: Withaferin A significantly inhibited the growth of GBM in vitro and in vivo and triggered the通过上调BIM和不良的表达,GBM细胞的内在凋亡。 WA通过激活p53无依赖的p21上调,在细胞周期的G2/m期通过去磷酸化的Throf Throf Throf Throf Throf Throf Throf Throne parter。击倒P21通过下调不良而不是BIM的表达来恢复细胞周期的进程和细胞活力。我们证明了WA通过ATF4-ATF3-CHOP轴诱导的内质网应力(ER)应力,在GBM细胞中启动凋亡和G2/M停滞。
结论: 我们揭示了一种新的途径,该途径通过ATF4-ATF3-ATF3-Chopis阐明了GBM细胞中凋亡和G2/M停滞的WA激活。该发现对于优化基于WA的方案以预防和/或治疗GBM很重要。