Parthenolide induces autophagy via the depletion of 4E-BP1
Parthenolide induces autophagy via the depletion of 4E-BP1
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小白菊内酯通过消耗 4E-BP1 诱导自噬
DOI：
10.1016/j.bbrc.2014.11.102
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发表时间：
2015
影响因子：
3.1
通讯作者：
Cao Youjia
中科院分区：
文献类型：
--
作者：
Lan Bei;Wan Ya-Juan;Pan Shuang;Wang Yu;Yang Yin;Leng Qian-Li;Jia Huiyan;Liu Yao-hui;Zhang Cui-Zhu;Cao Youjia
银胶菊（PTL）是从小白菊中分离的倍半萜内酯，并对各种癌症表现出有效的抗肿瘤活性。许多研究表明，PTL处理导致细胞凋亡，但其机制尚未明确。在这里，我们观察到细胞在PTL处理后不久发生自噬。通过敲除自噬相关基因g5抑制自噬可阻断PTL诱导的细胞凋亡。令人惊讶的是，PTL降低了与自噬相关的翻译起始因子eIF 4 E结合蛋白1（4 E-BP 1）的水平。4 E-BP 1的异位表达或shRNA敲低进一步验证了4 E-BP 1对PTL诱导的自噬的作用。同时，PTL还能增加4 E-BP 1缺失上游的细胞活性氧（reactive oxygen species，ROS），促进自噬。这项研究揭示了4 E-BP 1作为PTL诱导的自噬的触发因素，并可能导致提高抗癌药物疗效的治疗策略。
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 geneatg5 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.