化学
PI3K/AKT/mTOR通路
程序性细胞死亡
癌症研究
mTORC1型
细胞生长
ULK1
雷帕霉素的作用靶点
细胞周期
细胞周期检查点
作者
Bei Lan,Yajuan Wan,Shuang Pan,Yu Wang,Yin Yuan,Qianli Leng,Hui-Yan Jia,Yaohui Liu,Cuizhu Zhang,Youjia Cao
标识
DOI:10.1016/j.bbrc.2014.11.102
摘要
Parthenolide (PTL) is a sesquiterpene lactone isolated from feverfew and exhibits potent antitumor activity against various cancers. Many studies indicate that PTL treatment leads to apoptosis, however, the mechanism has not been defined. Here, we observed that cells underwent autophagy shortly after PTL treatment. Inhibition of autophagy by knocking out autophagy associated gene atg5 blocked PTL-induced apoptosis. Surprisingly, PTL decreased the level of translation initiation factor eIF4E binding protein 1 (4E-BP1) in correlation with autophagy. Ectopic expression or shRNA knockdown of 4E-BP1 further verified the effect of 4E-BP1 on PTL-induced autophagy. Meanwhile, PTL elevated the cellular reactive oxygen species (ROS) which located upstream of the depletion of 4E-BP1, and contributed to the consequent autophagy. This study revealed 4E-BP1 as a trigger for PTL-induced autophagy and may lead to therapeutic strategy to enhance the efficacy of anticancer drugs.
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