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

doi:10.1038/aps.2016.154

	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
	Peng, Chun1,2,3 ; Qi, Xin-ming 1,3; Miao, Ling-ling 1,3; Ren, Jin1,2,3
	2017-04
发表期刊	ACTA PHARMACOLOGICA SINICA (IF:6.9[JCR-2023],7.6[5-Year])
ISSN	1671-4083
卷号	38 期号:4 页码:561-570
发表状态	已发表
DOI	10.1038/aps.2016.154
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.
关键词	1,2:5,6-dianhydrogalactitol human glioblastoma cell cycle arrest p53-p21 cascade CDC25C-CDK1 cascade radiosensitivity xenografted tumors
收录类别	SCI
语种	英语
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
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号	WOS:000399192700011
出版者	ACTA PHARMACOLOGICA SINICA
WOS关键词	NEWLY-DIAGNOSED GLIOBLASTOMA ; DNA-DAMAGE ; RANDOMIZED-TRIAL ; DIANHYDROGALACTITOL ; TEMOZOLOMIDE ; P53 ; CANCER ; TUMORS ; BEVACIZUMAB ; COMBINATION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1439
专题	生命科学与技术学院_硕士生生命科学与技术学院生命科学与技术学院_特聘教授组_任进组
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
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
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.