Structures/cytotoxicity/selectivity relationship of natural steroidal saponins against GSCs and primary mechanism of tribulosaponin A

被引：10

作者：

Dai, Zhi ^{[1
]}

Liu, Hui ^{[2
]}

Wang, Bei ^{[2
]}

Yang, Dong ^{[3
]}

Zhu, Yan-Yan ^{[1
]}

Yan, Huan ^{[2
]}

Zhu, Pei-Feng ^{[2
]}

Liu, Ya-Ping ^{[2
]}

Chen, Hui-Cheng ^{[1
]}

Zhao, Yun-li ^{[1
]}

Zhao, Li-Xing ^{[1
]}

Zhao, Xu-Dong ^{[3
]}

Liu, Hai-Yang ^{[2
]}

Luo, Xiao-Dong ^{[1
,2
]}

机构：

[1] Yunnan Univ, Yunnan Prov Ctr Res & Dev Nat Prod, Sch Chem Sci & Technol, Key Lab Med Chem Nat Resource,Minist Educ, Kunming 650091, Yunnan, Peoples R China

[2] Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China

[3] Sichuan Univ, State Key Lab Biotherapy & Canc Ctr, Natl Clin Res Ctr Geriatr,West China Hosp, Lab Anim Tumor Models,Frontiers Sci Ctr Dis Relat, Chengdu 610041, Sichuan, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 210卷

基金：

中国国家自然科学基金;

关键词：

Steroidal saponins; Structure-activity relationship; Tribulosaponin A; Glioma stem cells; ROS; SMALL MOLECULES; CARDIAC-ARREST; STEM-CELL; IDENTIFICATION; THERAPY; BRAIN; OPPORTUNITIES; GLIOMA; NOX2;

D O I：

10.1016/j.ejmech.2020.113068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Glioblastoma multiform (GBM) is the highly aggressive brain tumor with poor prognosis. Glioma stem cells (GSCs), small population of cancer cells that exist in GBM tissues, resistant to chemotherapy and radiotherapy and usually driving GBM recurrence, have been developed as effective therapeutic target. Steroidal saponins are one of important resources for anti-tumor agent and may be benefited to selectively clear GSCs. In this report, total of 97 natural steroidal saponins were investigated the relationship among structures/cytotoxicity/selectivity against GSCs, glioma cell lines and human untransformed cells, and revealed that tribulosaponin A was the most potent compound. Further investigation suggested that tribulosaponin A up-regulated the expression of NCF1 and NOX1 to accumulate ROS for triggering apoptosis in GSCs, but not in untransformed cells, and it was further supported by the assay that N-acetyl-L-cysteine (NAC) clearing ROS delayed GSCs apoptosis. Besides, tribulosaponin A damaged GSCs recapturing tumor spheres formation. (C) 2020 Elsevier Masson SAS. All rights reserved.

引用

页数：10

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