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Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite

文献类型：期刊论文

作者Zhu, Yan2,3,4; Klausen, Christian4; Zhou, Jieyun2,3; Guo, Xiangjie2,3; Zhang, Yu1; Zhu, Hua4; Li, Zhao2,3; Cheng, Jung-Chien4; Xie, Shuwu2,3; Yang, Wenjie2,3
刊名SCIENTIFIC REPORTS
出版日期2019-10-29
卷号9页码:14
ISSN号2045-2322
DOI10.1038/s41598-019-52108-6
通讯作者Zhu, Yan(zhuyan@sippr.org) ; Leung, Peter C. K.(peter.leung@ubc.ca)
英文摘要In the present study, a novel dimer, SM1044, selected from a series of dihydroartemisinin (DHA) derivatives containing nitrogen atoms comprising simple aliphatic amine linkers, showed strong growth inhibition in six types of human endometrial cancer (EC) cells, with half maximal inhibitory concentration (IC50) and 95% confidence interval (CI) < 3.6 (1.16 similar to 11.23) mu M. SM1044 evoked apoptosis and activated caspase-3, -8 and -9 in a concentration- and time-dependent manner, and these effects were manifested early in RL95-2 compared to KLE cells, possibly correlated with the induction of intracellular ONOO-. Catalase and uric acid attenuated the growth inhibitory effects of SM1044 on EC cells, but sodium pyruvate did not. In vivo, the average xenograft tumour growth inhibition rates ranged from 35.8% to 49.9%, respectively, after 2.5 and 5.0 mg/kg SM1044 intraperitoneal treatment, and no obvious behavioural and histopathological abnormalities were observed in SM1044-treated mice in this context. SM1044 predominantly accumulated in the uteri of mice after a single injection. SM1044 displayed efficacy as a tumour suppressor with distinct mechanism of action and unique tissue distribution, properties that distinguish it from other artemisinin analogues. Our findings provide a new clue for artemisinin analogue against cancer.
WOS关键词ARTEMISININ DIMERS ; ORAL ARTESUNATE ; IN-VITRO ; PHASE-I ; ANTIMALARIAL ; CARCINOMA ; NEUROTOXICITY ; CYTOTOXICITY ; DERIVATIVES ; THERAPY
资助项目Canadian Institutes of Health Research[143317] ; Shanghai Science and Technology Innovation Action from Science and Technology Commission of Shanghai Municipality[14431901900] ; China scholarship Council[201508310018] ; Science and Technology Climbing Fund of SIPPR[PD2017-05] ; State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1903KF-11]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000493048400081
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/281802]  
专题中国科学院上海药物研究所
通讯作者Zhu, Yan; Leung, Peter C. K.
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Fudan Univ, Lab Reprod Pharmacol, Shanghai Inst Planned Parenthood Res, Shanghai 200032, Peoples R China
3.Fudan Univ, Key Lab Reprod Regulat NPFPC, SIPPR, IRD, Shanghai 200032, Peoples R China
4.Univ British Columbia, BC Childrens Hosp Res Inst, Dept Obstet & Gynaecol, Vancouver, BC V5Z 4H4, Canada
推荐引用方式
GB/T 7714		 Zhu, Yan,Klausen, Christian,Zhou, Jieyun,et al. Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite[J]. SCIENTIFIC REPORTS,2019,9:14.
APA Zhu, Yan.,Klausen, Christian.,Zhou, Jieyun.,Guo, Xiangjie.,Zhang, Yu.,...&Leung, Peter C. K..(2019).Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite.SCIENTIFIC REPORTS,9,14.
MLA Zhu, Yan,et al."Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite".SCIENTIFIC REPORTS 9(2019):14.

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来源：上海药物研究所

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