期刊
TOXINS
卷 9, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/toxins9050150
关键词
melodinus suaveolens; indole alkaloid; 3 alpha-acetonyltabersonine; glioblastoma; cell apoptosis; DNA damage repair
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA 01040403]
- Top Talents Program of Yunnan Province, China [2012 HA014]
- Yunnan Applied Basic Research Projects [2013FA020]
- National Natural Science Foundation of China [81225024]
- CAS Light of West China Program & Yunnan Provincial Department of education [2017ZZX150]
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, 3 alpha-acetonyltabersonine, which was isolated from Melodinus suaveolens. 3 alpha-acetonyltabersonine was cytotoxic to glioblastoma cell lines (U87 and T98G) and stem cells at low concentrations. We verified 3 alpha-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 3 alpha-acetonyltabersonine treatment. Additionally, we found 3 alpha-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 3 alpha-acetonyltabersonine could exert pro-apoptotic function and prolong the life span of tumor-bearing mice. These results in vitro and in vivo suggested that 3 alpha-acetonyltabersonine could be a potential candidate antitumor agent.
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