2. Academic Validation
  3. Structures/cytotoxicity/selectivity relationship of natural steroidal saponins against GSCs and primary mechanism of tribulosaponin A

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

  • Eur J Med Chem. 2021 Jan 15:210:113068. doi: 10.1016/j.ejmech.2020.113068.
Zhi Dai 1,  Hui Liu 2,  Bei Wang 2,  Dong Yang 3,  Yan-Yan Zhu 1,  Huan Yan 2,  Pei-Feng Zhu 2,  Ya-Ping Liu 2,  Hui-Cheng Chen 1,  Yun-Li Zhao 1,  Li-Xing Zhao 1,  Xu-Dong Zhao 4,  Hai-Yang Liu 5,  Xiao-Dong Luo 6
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China.
  • 3 Laboratory of Animal Tumor Models, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
  • 4 Laboratory of Animal Tumor Models, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China. Electronic address: zhaoxudong@wchscu.cn.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China. Electronic address: haiyangliu@mail.kib.ac.cn.
  • 6 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China. Electronic address: xdluo@mail.kib.ac.cn.
PMID: 33310292 DOI: 10.1016/j.ejmech.2020.113068
Abstract

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.

Keywords

Glioma stem cells; ROS; Steroidal saponins; Structure-activity relationship; Tribulosaponin A.

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