Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair

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	Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair
	Li Y 1,3,4,5; Zhao YL 2; Yang D 1; Hao JJ 7; Luo L 6; Liu YP 2; Luo XD[]2; Zhao XD[]1,8; Zhou X 1,3,4; Ni W 6
刊名	Toxins
	2017
卷号	9 期号:X 页码:e150
关键词	melodinus suaveolens indole alkaloid 3 α -acetonyltabersonine glioblastoma cell apoptosis DNA damage repair
通讯作者	xdluo@mail.kib.ac.cn ; zhaoxudong@mail.kiz.ac.cn
英文摘要	Cytotoxic indole alkaloids from Melodinus suaveolens, which belongs to the toxic plant family Apocynaceae, demonstrated impressive antitumor activities in many tumor types, but less application in glioblastoma, which is the lethal brain tumor. In the present study, we reported the anti-glioblastoma activity of an indole alkaloid, 3α-acetonyltabersonine, which was isolated from Melodinus suaveolens. 3α-acetonyltabersonine was cytotoxic to glioblastoma cell lines (U87 and T98G) and stem cells at low concentrations. We verified 3α-acetonyltabersonine could suppress tumor cell proliferation and cause apoptosis in glioblastoma stem cells (GSCs). Moreover, detailed investigation of transcriptome study and Western blotting analysis indicated the mitogen activated protein kinase (MAPK) pathway was activated by phosphorylation upon 3α-acetonyltabersonine treatment. Additionally, we found 3α-acetonyltabersonine inhibited DNA damage repair procedures, the accumulated DNA damage stimulated activation of MAPK pathway and, finally, induced apoptosis. Further evidence was consistently obtained from vivo experiments on glioblastoma mouse model: treatment of 3α-acetonyltabersonine could exert pro-apoptotic function and prolong the life span of tumor-bearing mice. These results in vitro and in vivo suggested that 3α-acetonyltabersonine could be a potential candidate antitumor agent.
收录类别	SCI
资助信息	This work was jointly supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA 01040403 to Xudong Zhao); the Top Talents Program of Yunnan Province, China (2012 HA014 to Xudong Zhao); Yunnan Applied Basic Research Projects (2013FA020 to Xudong Zhao); the National Natural Science Foundation of China (No. 81225024 to Xiaodong Luo) and CAS “Light of West China”Program &Yunnan Provincial Department of education funded projects (No. 2017ZZX150 to Yuan Li).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/11238]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_基因起源组昆明动物研究所_进化与功能基因组学昆明动物研究所_中国科学院昆明灵长类研究中心
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 21 Qingsong Road, Kunming 650203, China 2.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Kunming 650201, China 3.Kunming College of Life Science, University of Chinese Academy of Sciences, 19 Qingsong Road, Kunming 650203, China 4.Graduate School, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China 5.Division of Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Kunming 650500, China 6.Department of Neurosurgery, Tumor Hospital of Yunnan Province, 519 Kunzhou Road, Kunming 650000, China 7.State Key Lab of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 21 Qingsong Road, Kunming 650203, China 8.Kunming Primate Research Center, Chinese Academy of Sciences, 32 East Jiaochang Road, Kunming 650223, China
推荐引用方式 GB/T 7714	Li Y,Zhao YL,Yang D,et al. Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair[J]. Toxins,2017,9(X):e150.
APA	Li Y.,Zhao YL.,Yang D.,Hao JJ.,Luo L.,...&Dai Z.(2017).Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair.Toxins,9(X),e150.
MLA	Li Y,et al."Cytotoxic Indole Alkaloid 3α-Acetonyltabersonine Induces Glioblastoma Apoptosis via Inhibition of DNA Damage Repair".Toxins 9.X(2017):e150.