Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells

doi:10.1093/abbs/gmaa009

	Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells
	Xi, Mengyu 2,4; He, Wan 3; Li, Bo 2,4; Zhou, Jinfeng 3; Xu, Zhijian 2,4; Wu, Huiqun 3; Zhang, Yong 2,4; Song, Dongliang 3; Hu, Liangning 3; Lu, Ye 1
刊名	ACTA BIOCHIMICA ET BIOPHYSICA SINICA
	2020-04-01
卷号	52 期号:4 页码:401-410
关键词	DCZ0801 DLBCL apoptosis cell cycle MAPK
ISSN号	1672-9145
DOI	10.1093/abbs/gmaa009
通讯作者	Li, Bo(boli@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要	Diffuse large B-cell lymphoma (DLBCL) is the most common category and disease entity of non-Hodgkin lymphoma. Osalmide and pterostilbene are natural products with anticancer activities via different mechanism. In this study, using a new synthetic strategy for the two natural products, we obtained the compound DCZ0801, which was previously found to have anti-multiple myeloma activity. We performed both in vitro and in vivo assays to investigate its bioactivity and explore its underlying mechanism against DLBCL cells. The results showed that DCZ0801 treatment gave rise to a dose- and time-dependent inhibition of cell viability as determined by CCK-8 assay and flow cytometry assay. Western blot analysis results showed that the expression of caspase-3, caspase-8, caspase-9 and Bax was increased, while BCL-2 and BCL-XL levels were decreased, which suggested that DCZ0801 inhibited cell proliferation and promoted intrinsic apoptosis. In addition, DCZ0801 induced G0/G1 phase arrest by downregulating the protein expression levels of CDK4, CDK6 and cyclin D1. Furthermore, DCZ0801 exerted an anti-tumor effect by down-regulating the expressions of p-PI3K and p-AKT. There also existed a trend that the expression of p-JNK and p-P38 was restrained. Intraperitoneal injection of DCZ0801 suppressed tumor development in xenograft mouse models. The preliminary metabolic study showed that DCZ0801 displayed a rapid metabolism within 30 min. These results demonstrated that DCZ0801 may be a new potential anti-DLBCL agent in DLBCL therapy.
资助项目	National Science & Technology Major Project `Key New Drug Creation and Manufacturing Program'[2018ZX09711002] ; National Natural Science Foundation of China[81603270] ; National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81670194]
WOS关键词	SIGNALING PATHWAY ; P38 MAPK ; JNK ; APOPTOSIS ; PROLIFERATION ; PI3K/AKT/MTOR ; HETEROGENEITY ; MECHANISMS ; AUTOPHAGY ; CANCER
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000544987800007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291982]
专题	中国科学院上海药物研究所
通讯作者	Li, Bo; Shi, Jumei; Zhu, Weiliang
作者单位	1.Soochow Univ, Dept Hematol & Oncol, Peoples Hosp Taicang 1, Affiliated Taicang Hosp, Suzhou 215400, Jiangsu, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China 4.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Xi, Mengyu,He, Wan,Li, Bo,et al. Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2020,52(4):401-410.
APA	Xi, Mengyu.,He, Wan.,Li, Bo.,Zhou, Jinfeng.,Xu, Zhijian.,...&Zhu, Weiliang.(2020).Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,52(4),401-410.
MLA	Xi, Mengyu,et al."Novel cyclophosphamide of natural products osalmide and pterostilbene induces cytotoxicity and cell cycle arrest in diffuse large B-cell lymphoma cells".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 52.4(2020):401-410.