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The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo
Guo, Chuanlong1,2; Hou, Yuzhen1,2; Yu, Xuemin3; Zhang, Fan1,2; Wu, Xiaochen1,2; Wu, Xianggen1,2; Wang, Lijun4
2020-03-01
Source PublicationFOOD AND CHEMICAL TOXICOLOGY
ISSN0278-6915
Volume137Pages:10
Corresponding AuthorWu, Xianggen(wuxianggen@126.com) ; Wang, Lijun(wanglijun@qdio.ac.cn)
AbstractThe eIF4E/eIF4G complex plays a central role in gene expression regulation during the initial stage of translation. This study aimed to determine if the novel small molecule compound, TPDHT, could disrupt the interaction of eIF4E/eIF4G, and if it could exhibit excellent antitumor activity in vivo without causing apparent toxicity effect. This study investigated the antitumor mechanism of TPDHT in vitro and in vivo. TPDHT showed significant anti-proliferative activity on human lung cancer A549 cells, and it induced G0/G1 cycle arrest. Moreover, TPDHT also induced A549 cell apoptosis through the mitochondria-mediated apoptotic pathway. Our results indicate that TPDHT could disrupt the interaction of eIF4E/eIF4G, and the activity of eIF4F plays an important role in TPDHT-induced cell proliferation inhibition and apoptosis. Further research showed that TPDHT could inhibit the Ras/ERK/MNK pathway, and activation of the ERK pathway reversed TPDHT-induced cell proliferation inhibition and apoptosis. Taken together, our study findings indicated that TPDHT exerts an antitumor effect through an intrinsic apoptotic pathway controlled by the ERK/MNK/eIF4F pathway.
KeywordApoptosis eIF4F ERK MNK A549 cells
DOI10.1016/j.fct.2020.111158
Indexed BySCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81773586] ; Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering[XTCXQN19]
WOS Research AreaFood Science & Technology ; Toxicology
WOS SubjectFood Science & Technology ; Toxicology
WOS IDWOS:000517659300016
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/165632
Collection实验海洋生物学重点实验室
Corresponding AuthorWu, Xianggen; Wang, Lijun
Affiliation1.Qingdao Univ Sci & Technol, Coll Chem Engn, Dept Pharm, Qingdao 266042, Peoples R China
2.Qingdao Univ Sci & Technol, Key Lab Pharmaceut Res Metab Dis, Qingdao, Peoples R China
3.Shandong Univ, Qilu Hosp, NHC Key Lab Otorhinolaryngol, Dept Otorhinolaryngol, Shandong 266035, Peoples R China
4.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China
Corresponding Author AffilicationKey Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Guo, Chuanlong,Hou, Yuzhen,Yu, Xuemin,et al. The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo[J]. FOOD AND CHEMICAL TOXICOLOGY,2020,137:10.
APA Guo, Chuanlong.,Hou, Yuzhen.,Yu, Xuemin.,Zhang, Fan.,Wu, Xiaochen.,...&Wang, Lijun.(2020).The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo.FOOD AND CHEMICAL TOXICOLOGY,137,10.
MLA Guo, Chuanlong,et al."The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo".FOOD AND CHEMICAL TOXICOLOGY 137(2020):10.
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