title: Parthenolide induces autophagy via the depletion of 4E-BP1.
abstract: 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.
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Lan
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wan
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Pan
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Leng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
authors.forename: Yao-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China. Electronic address: czz912@aliyun.com.
authors.forename: Cui-Zhu
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Microbial Functional Genomics of Ministry of Education, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, PR China. Electronic address: caoyj@nankai.edu.cn.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D039642:Eukaryotic Initiation Factors; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010588:Phagosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010957:Plasmids; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C002669:parthenolide
keywords: 4E-BP1; Apoptosis; Autophagy; Parthenolide; Reactive oxygen species