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1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G(2)/M phase

文献类型：期刊论文

作者Peng, Chun1,2,3; Qi, Xin-ming1,3; Miao, Ling-ling1,3; Ren, Jin1,2,3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2017-04
卷号38期号:4页码:561-570
关键词1,2:5,6-dianhydrogalactitol human glioblastoma cell cycle arrest p53-p21 cascade CDC25C-CDK1 cascade radiosensitivity xenografted tumors
ISSN号1671-4083
DOI10.1038/aps.2016.154
文献子类Article
英文摘要1,2:5,6-dianhydrogalactitol (DAG) is a hexitol epoxide with marked antitumor activity against multiple types of cancer cells, but the molecular mechanisms by which DAG functions as an antitumor agent is largely unknown. In this study, we investigated the inhibitory effects of DAG on human glioma cell growth in vitro and in vivo and uncovered the underlying molecular mechanisms. Treatment with DAG (120 mu mol/L) dose-dependently inhibited the proliferation and colony formation in human glioma cell lines LN229, U251, and U87MG in vitro. DAG (1, 2, 5 mu mol/L) induced cell cycle arrest at G(2)/M phase in the 3 glioma cell lines in a dose-dependent manner. The signaling pathways involved in DAG-caused cell cycle arrest was further analyzed in LN229 cells, which revealed that DAG dose-dependently activated two parallel signaling cascades, ie, the p53-p21 cascade and the CDC25C-CDK1 cascade. DAG also significantly enhanced the radiosensitivity of LN229 cells as shown in the clonogenic assay. In nude mice bearing subcutaneously xenografted LN229 glioma, administration of DAG (5 mg/kg, iv, twice per week for 6 weeks) effectively suppressed the growth of xenografted tumors: the relative tumor growth rate (T/C) was reduced to 22.38%, and the tumor growth inhibitory rate (TGI) was 83.58% (P< 0.01). In addition, DAG administration significantly activated the CDC25C-CDK1 cascade in the xenografted tumors. In conclusion, DAG inhibited human glioma cell growth in vitro and in vivo by inducing cell cycle arrest at G2/M phase. Two parallel cascades are activated and involved in the cell cycle arrest.
WOS关键词NEWLY-DIAGNOSED GLIOBLASTOMA ; DNA-DAMAGE ; RANDOMIZED-TRIAL ; DIANHYDROGALACTITOL ; TEMOZOLOMIDE ; P53 ; CANCER ; TUMORS ; BEVACIZUMAB ; COMBINATION
资助项目National Science and Technology Major Project[2012ZX09302-003] ; National Science and Technology Major Project[2015ZX09102005]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5953665
WOS记录号WOS:000399192700011
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/272727]  
专题药物安全性评价中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Miao, Ling-ling; Ren, Jin
作者单位1.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;
3.Univ Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Peng, Chun,Qi, Xin-ming,Miao, Ling-ling,et al. 1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G(2)/M phase[J]. ACTA PHARMACOLOGICA SINICA,2017,38(4):561-570.
APA Peng, Chun,Qi, Xin-ming,Miao, Ling-ling,&Ren, Jin.(2017).1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G(2)/M phase.ACTA PHARMACOLOGICA SINICA,38(4),561-570.
MLA Peng, Chun,et al."1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G(2)/M phase".ACTA PHARMACOLOGICA SINICA 38.4(2017):561-570.

入库方式： OAI收割

来源：上海药物研究所

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