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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
Source PublicationPHYTOMEDICINE
ISSN0944-7113
Volume48Pages:170-178
AbstractBackground: 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.
KeywordGlioma stem cells Antitumor activity Alstonia scholaris Nor-monoterpenoid indole alkaloids
DOI10.1016/j.phymed.2018.04.057
Language英语
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000443714600019
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/62227
Collection中国科学院昆明植物研究所
Corresponding AuthorWang, Xin-Hua; Zhao, Xu-Dong; Luo, Xiao-Dong
Affiliation1.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
Recommended Citation
GB/T 7714
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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