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

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.

• Authors: Zhi Dai, Hui Liu, Bei Wang, Dong Yang, Yan-Yan Zhu, Huan Yan, Pei-Feng Zhu, Ya-Ping Liu, Hui-Cheng Chen, Yun-Li Zhao, Li-Xing Zhao, Xu-Dong Zhao, Hai-Yang Liu, Xiao-Dong Luo
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 210 Pg. 113068 (Jan 15 2021) ISSN: 1768-3254 [Electronic] France
• PMID: 33310292 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biological Products
• GSC protein, human
• Goosecoid Protein
• Saponins

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Biological Products (chemical synthesis, chemistry, pharmacology)
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Glioblastoma (drug therapy, metabolism, pathology)
• Goosecoid Protein (antagonists & inhibitors, metabolism)
• Humans
• Molecular Structure
• Saponins (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured