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Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris
Wang, Bei1,3; Dai, Zhi2,3; Yang, Xiong-Wu1,3; Liu, Ya-Ping1; Khan, Afsar5; Yang, Zi-Feng4; Huang, Wan-Yi4; Wang, Xin-Hua4; Zhao, Xu-Dong2; Luo, Xiao-Dong1,4
2018-09-15
发表期刊PHYTOMEDICINE
ISSN0944-7113
卷号48页码:170-178
摘要Background: Glioblastoma multiforme (GBM) is a highly aggressive and frequently recurrent malignant brain tumor, and to date, the clinically effective drugs against GBM remain scarce. Natural products play an important role in drug discovery, and might be the resource of antitumor agents for GSCs. Alstonia scholaris (L.) R. Br. is rich in monoterpenoid indole alkaloids (MIAs) and used extensively for treatment of tumor in the traditional medicine system of Asia. Purpose: To search for new MIAs with antitumor activity against glioma stem cells from clinical patients and explore their mechanism. Methods: Compounds were obtained from the fruits of A. scholaris by chromatographic separation, including silica gel, Sephadex LH-20 and recrystallization. Their structures were elucidated by the use of UV, IR, NMR and MS spectra. The antitumor activity of the compounds against the glioma stem cells (GSC-3#, GSC-12#, GSC-18#) were investigated by phenotypic screening and MTS assays. Cell proliferation assay by BrdU immunofluorescence staining, and apoptosis assay by cleaved-caspase-3 immunofluorescence staining and real-time PCR assay. The soft-agar clonal formation assay was performed to determine the antitumor efficacy of the compounds in vitro. Results: Two new nor-monoterpenoid indole alkaloids were isolated from the fruits of A. scholaris. They exhibited selective antitumor activity against glioma stem cells (GSC-3#, GSC-12#, GSC-18#) with IC50 values of 15-25 mu g/ml. Furthermore, they inhibited GSCs proliferation, induced GSC5 apoptosis by increasing the expression of TNF-alpha and cleavage of caspase-3, and significantly damaged colony forming capacity of GSCs. Conclusion: New nor-monoterpenoid indole alkaloids from the fruits of A. scholaris provide new type promising molecule for the selective killing of human glioma stem cells.
关键词Glioma stem cells Antitumor activity Alstonia scholaris Nor-monoterpenoid indole alkaloids
资助信息NSFC; National Key Research and Development Program of China
DOI10.1016/j.phymed.2018.04.057
语种英语
资助项目NSFC[31770388] ; NSFC[81225024] ; NSFC[31500292] ; National Key Research and Development Program of China[SQ2017YFC170594-07]
WOS研究方向Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS类目Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS记录号WOS:000443714600019
出版者ELSEVIER GMBH, URBAN & FISCHER VERLAG
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/62227
专题中国科学院昆明植物研究所
通讯作者Wang, Xin-Hua; Zhao, Xu-Dong; Luo, Xiao-Dong
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mechanisms, Key Lab Bioact Peptides Yunnan Prov, Prov Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China
5.COMSATS Inst Informat Technol, Dept Chem, Abbottabad 22060, Pakistan
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Wang, Bei,Dai, Zhi,Yang, Xiong-Wu,et al. Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris[J]. PHYTOMEDICINE,2018,48:170-178.
APA Wang, Bei.,Dai, Zhi.,Yang, Xiong-Wu.,Liu, Ya-Ping.,Khan, Afsar.,...&Luo, Xiao-Dong.(2018).Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris.PHYTOMEDICINE,48,170-178.
MLA Wang, Bei,et al."Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris".PHYTOMEDICINE 48(2018):170-178.
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