DCZ3301, a novel aryl-guanidino inhibitor, induces cell apoptosis and cell cycle arrest via suppressing the PI3K/AKT pathway in T-cell leukemia/lymphoma

doi:10.1093/abbs/gmy047

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	DCZ3301, a novel aryl-guanidino inhibitor, induces cell apoptosis and cell cycle arrest via suppressing the PI3K/AKT pathway in T-cell leukemia/lymphoma
	Xiao, Wenqin 1; Li, Bo 2; Sun, Xi 1; Yu, Dandan 1; Xie, Yongsheng 1; Wu, Huiqun 1; Chang, Shuaikang 1; Zhou, Yunfei 2; Wang, Houcai 1; Lan, Xiucai 1
刊名	ACTA BIOCHIMICA ET BIOPHYSICA SINICA
	2018-07
卷号	50 期号:7 页码:643-650
关键词	DCZ3301 T-cell leukemia/lymphoma apoptosis cell cycle PI3K/AKT
ISSN号	1672-9145
DOI	10.1093/abbs/gmy047
文献子类	Article
英文摘要	DCZ3301, a novel aryl-guanidino compound, was previously found to have potent anti-tumor activity in myeloma and B-cell lymphoma. In the present study, we investigated the effects of DCZ3301 on T-cell leukemia/lymphoma cells both in vitro and in vivo via cell proliferation, cell cycle analysis, apoptosis assay, mitochondrial membrane potential (MMP) assay, western blot analysis and tumor xenograft models. We found that DCZ3301 inhibited the viability of T-cell leukemia/lymphoma cells in a dose-and time-dependent manner. DCZ3301-induced G2/M cell cycle arrest, associated with downregulation of CDK1, cyclin B1, and cdc25C. DCZ3301 also induced cell apoptosis by decreasing MMP in T-cell leukemia/lymphoma cells, but had no significant pro-apoptotic effect on normal peripheral blood mononuclear cells (PBMCs). In addition, DCZ3301-induced apoptosis may be mediated by the caspase-dependent pathway and suppressing the phosphoinositide 3-kinase (PI3K)/AKT pathway. Finally, we showed that DCZ3301 treatment effectively inhibited tumor growth, with no significant side effects, in xenograft mouse models. In conclusion, these results suggest that DCZ3301 may be regarded as a new therapeutic strategy for T-cell leukemia/lymphoma patients.
资助项目	National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81570190] ; National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81600174]
WOS关键词	ACUTE LYMPHOBLASTIC-LEUKEMIA ; NON-HODGKIN-LYMPHOMA ; SIGNALING PATHWAYS ; DEATH ; PROTEIN ; LINES
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
CSCD记录号	CSCD:6325924
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000438251600003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279680]
专题	药物发现与设计中心
通讯作者	Shi, Jumei; Zhu, Weiliang
作者单位	1.Tongji Univ, Dept Hematol, Shanghai Peoples Hosp 10, Sch Med, Shanghai 200072, Peoples R China; 2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res,Drug Discovery & Design, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xiao, Wenqin,Li, Bo,Sun, Xi,et al. DCZ3301, a novel aryl-guanidino inhibitor, induces cell apoptosis and cell cycle arrest via suppressing the PI3K/AKT pathway in T-cell leukemia/lymphoma[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2018,50(7):643-650.
APA	Xiao, Wenqin.,Li, Bo.,Sun, Xi.,Yu, Dandan.,Xie, Yongsheng.,...&Zhu, Weiliang.(2018).DCZ3301, a novel aryl-guanidino inhibitor, induces cell apoptosis and cell cycle arrest via suppressing the PI3K/AKT pathway in T-cell leukemia/lymphoma.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,50(7),643-650.
MLA	Xiao, Wenqin,et al."DCZ3301, a novel aryl-guanidino inhibitor, induces cell apoptosis and cell cycle arrest via suppressing the PI3K/AKT pathway in T-cell leukemia/lymphoma".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 50.7(2018):643-650.