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.

胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，预后较差。胶质瘤干细胞（GSC）是存在于GBM组织中的少数癌细胞，对化学疗法和放射疗法具有抵抗力，通常会导致GBM复发，已被开发为有效的治疗靶标。甾体皂苷是抗肿瘤药的重要资源之一，可能有利于选择性清除GSC。在这份报告中，总共研究了97种天然甾体皂苷对结构，细胞毒性/针对GSC，神经胶质瘤细胞系和人类未转化细胞的选择性之间的关系，并揭示了三皂甙A是最有效的化合物。进一步的研究表明，三叶皂苷A上调NCF1和NOX1的表达，从而积累ROS来触发GSC的细胞凋亡，N-乙酰基-1-半胱氨酸（NAC）清除ROS延迟GSCs凋亡。此外，三叶皂苷A破坏了GSC，重新捕获了肿瘤球的形成。