Novel eIF4E/eIF4G protein-protein interaction inhibitors DDH-1 exhibits anti-cancer activity in vivo and in vitro

doi:10.1016/j.ijbiomac.2020.05.233

IOCAS-IR > 实验海洋生物学重点实验室

	Novel eIF4E/eIF4G protein-protein interaction inhibitors DDH-1 exhibits anti-cancer activity in vivo and in vitro
	Wang, Jun 1; Wang, Lijun 2; Zhang, Shuhong 3; Fan, Junting 4; Yang, Hui1 ; Li, Qiqi 1; Guo, Chuanlong 1
	2020-10-01
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
ISSN	0141-8130
卷号	160 页码:496-505
通讯作者	Guo, Chuanlong(guochuanlong@qust.edu.cn)
摘要	(E)-2-(2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazinyl)-4-(3,4-difluorophenyl) thiazole (DDH-1) is novel small molecule compound synthesized in our previous work. This study found that DDH-1 could inhibit the proliferation of various human lung cancer cells. Particularly, the IC50 for A549 cells was 8.59 AM. Interestingly, we found that DDH-1 inhibits eIF4E/eIF4G interaction. The flow cytometry (FAGS) results have indicated that DDH-1 may induce G0/G1 cycle arrest by inhibiting the expression of Cyclin D1 and CDK4. DDH-1 may also cause apoptosis through the caspase-dependent pathway. Study of these mechanisms has shown that DDH-1 may prompt reactive oxygen species (ROS) generation, decrease the mitochondrial membrane potential (MMP), and stimulate DNA double-strand breaks (DSBs) in A549 cells. Study of the signal pathway has indicated that DDH-1 could activate JNK phosphorylation and inhibit ERK phosphorylation. Interestingly, NAC, which scavenges ROS, reversed the MMP decline, DNA damage, JNK phosphorylation activation, and ERK phosphorylation inhibition caused by DDH-1. Overall, these findings provide evidence that the eIF4E/eIF4G interaction inhibitors DDH-1 induces DNA damage and apoptosis in human lung cancer A549 cells. (C) 2020 Elsevier B.V. All rights reserved.
关键词	eIF4E/eIF4G Human lung cancer Apoptosis DNA damage ROS
DOI	10.1016/j.ijbiomac.2020.05.233
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81773586]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Applied ; Polymer Science
WOS记录号	WOS:000564748800017
出版者	ELSEVIER
引用统计	被引频次：8[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/337002/168508
专题	实验海洋生物学重点实验室
通讯作者	Guo, Chuanlong
作者单位	1.Qingdao Univ Sci & Technol, Coll Chem Engn, Dept Pharm, Qingdao 266042, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, CAS Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 3.Qingdao Chengyang Peoples Hosp, Qingdao 266109, Peoples R China 4.Nanjing Med Univ, Sch Pharm, Dept Pharmaceut Anal, Nanjing 211166, Peoples R China
推荐引用方式 GB/T 7714	Wang, Jun,Wang, Lijun,Zhang, Shuhong,et al. Novel eIF4E/eIF4G protein-protein interaction inhibitors DDH-1 exhibits anti-cancer activity in vivo and in vitro[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2020,160:496-505.
APA	Wang, Jun.,Wang, Lijun.,Zhang, Shuhong.,Fan, Junting.,Yang, Hui.,...&Guo, Chuanlong.(2020).Novel eIF4E/eIF4G protein-protein interaction inhibitors DDH-1 exhibits anti-cancer activity in vivo and in vitro.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,160,496-505.
MLA	Wang, Jun,et al."Novel eIF4E/eIF4G protein-protein interaction inhibitors DDH-1 exhibits anti-cancer activity in vivo and in vitro".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 160(2020):496-505.

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