DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway

doi:10.1038/cddis.2017.472

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway
	Sun, Xi 1,3; Li, Bo 2; Xie, Bingqian 3; Xu, Zhijian2 ; Chang, Gaomei 3; Tao, Yi 3; Zhang, Yong 2; Chang, Shuaikang 3; Wang, Yingcong 3; Yu, Dandan 3
刊名	CELL DEATH & DISEASE
	2017-10
卷号	8
ISSN号	2041-4889
DOI	10.1038/cddis.2017.472
文献子类	Article
英文摘要	Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential. DCZ3301 exerted an antitumor effect through modulation of Akt, extracellular signal-regulated kinases 1/2 (ERK1/2) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. Furthermore, DCZ3301 downregulates STAT3 phosphorylation by inhibiting Lck/Yes-related novel protein tyrosine kinase (Lyn) activation in DLBCL. A synergistic cytotoxic effect on DLBCL cells was observed upon combination of DCZ3301 with panobinostat. In vivo, intraperitoneal injection of xenograft mice with DCZ3301 resulted in reduced tumor volume. Our preliminary results collectively support the utility of the small-molecule inhibitor DCZ3301 as an effective novel therapeutic option for DLBCL that requires further clinical evaluation.
资助项目	National Natural Science Foundation of China[81372391] ; National Natural Science Foundation of China[81570190] ; National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81600174]
WOS关键词	PROTEIN-TYROSINE KINASE ; HEMATOPOIETIC-CELLS ; SIGNALING PATHWAY ; CYCLE ARREST ; R-CHOP ; ACTIVATION ; APOPTOSIS ; LYN ; EXPRESSION ; SURVIVAL
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000414022900048
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272463]
专题	药物发现与设计中心
通讯作者	Shi, Jumei; Zhu, Weiliang
作者单位	1.Nanjing Med Univ, Sch Clin Med, Nanjing 210000, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Tongji Univ, Sch Med, Canc Ctr, Shanghai Peoples Hosp 10,Dept Hematol, 301 Yanchang Rd, Shanghai 200072, Peoples R China;
推荐引用方式 GB/T 7714	Sun, Xi,Li, Bo,Xie, Bingqian,et al. DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway[J]. CELL DEATH & DISEASE,2017,8.
APA	Sun, Xi.,Li, Bo.,Xie, Bingqian.,Xu, Zhijian.,Chang, Gaomei.,...&Zhu, Weiliang.(2017).DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway.CELL DEATH & DISEASE,8.
MLA	Sun, Xi,et al."DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway".CELL DEATH & DISEASE 8(2017).