The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo

doi:10.1016/j.fct.2020.111158

IOCAS-IR > 实验海洋生物学重点实验室

	The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo
	Guo, Chuanlong 1,2; Hou, Yuzhen 1,2; Yu, Xuemin 3; Zhang, Fan 1,2; Wu, Xiaochen 1,2; Wu, Xianggen 1,2; Wang, Lijun 4
	2020-03-01
发表期刊	FOOD AND CHEMICAL TOXICOLOGY
ISSN	0278-6915
卷号	137 页码:10
通讯作者	Wu, Xianggen(wuxianggen@126.com) ; Wang, Lijun(wanglijun@qdio.ac.cn)
摘要	The 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.
关键词	Apoptosis eIF4F ERK MNK A549 cells
DOI	10.1016/j.fct.2020.111158
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81773586] ; Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering[XTCXQN19]
WOS研究方向	Food Science & Technology ; Toxicology
WOS类目	Food Science & Technology ; Toxicology
WOS记录号	WOS:000517659300016
出版者	PERGAMON-ELSEVIER SCIENCE LTD
引用统计	被引频次：10[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/165632
专题	实验海洋生物学重点实验室
通讯作者	Wu, Xianggen; Wang, Lijun
作者单位	1.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
通讯作者单位	实验海洋生物学重点实验室
推荐引用方式 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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