A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling

	A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling
	Bu, Wenxuan 1,2; Li, Bo 3; Feng, Lijin 4; Feng, Qilin 2; Hu, Ke 1; Xu, Zhijian 3; Wang, Yingcong 2; Xi, Mengyu 3; Wang, Houcai 2; Yang, Guang 2
刊名	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
	2021
卷号	13 期号:10 页码:11439-11449
关键词	Multiple myeloma DCZ0858 mTOR bone marrow microenvironment cell proliferation cell apoptosis
ISSN号	1943-8141
通讯作者	Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn)
英文摘要	Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of clonal plasma cells. Based on the organic drug osalmid, the novel small molecule compound DCZ0858 was designed and synthesized for treating MM. DCZ0858 inhibited the proliferation and activity of MM cells and reduced colony formation. It also promoted the apoptosis of primary cells from patients with MM and cultured MM cell lines but had little effect on peripheral blood mononuclear cells in healthy people. Simultaneously, DCZ0858 activated caspase family proteins, blocked MM cells in G0/G1 phase, and reduced the expression of related cyclins CDK4/6 and CyclinD1. Moreover, DCZ0858 overcame the protective effect of the bone marrow microenvironment and effectively inhibited the activity of mTORC1 and mTORC2. Further, xenograft model experiments in mice showed that DCZ0858 significantly inhibited the proliferation and growth of tumors, with low drug toxicity. These results indicate that DCZ0858 has marked anti-MM activity and little effect on normal cells and tissues, making it a new candidate clinical drug for the treatment of MM.
资助项目	National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81870158] ; National Natural Science Foundation of China[81900210] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Natural Science Foundation of Shanghai, China[19ZR1467800]
WOS关键词	BEVACIZUMAB ; SURVIVAL ; PET
WOS研究方向	Oncology ; Research & Experimental Medicine
语种	英语
出版者	E-CENTURY PUBLISHING CORP
WOS记录号	WOS:000714690100013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298677]
专题	中国科学院上海药物研究所
通讯作者	Zhu, Weiliang; Shi, Jumei
作者单位	1.Nanjing Med Univ, Nanjing 211100, Peoples R China 2.Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Hematol, 301 Yanchang Rd, Shanghai 200072, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, Sch Med, Shanghai 200072, Peoples R China
推荐引用方式 GB/T 7714	Bu, Wenxuan,Li, Bo,Feng, Lijin,et al. A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling[J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,2021,13(10):11439-11449.
APA	Bu, Wenxuan.,Li, Bo.,Feng, Lijin.,Feng, Qilin.,Hu, Ke.,...&Shi, Jumei.(2021).A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling.AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH,13(10),11439-11449.
MLA	Bu, Wenxuan,et al."A novel silicone derivative of natural osalmid (DCZ0858) exerts anti-multiple myeloma activity by promoting cell apoptosis and inhibiting cell cycle and mTOR signaling".AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 13.10(2021):11439-11449.