School of Pharmacy, Shaanxi University of Chinese Medicine, Air Force Medical University, Xi'an, P. R. China.
Institute of Materia Medica, Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Air Force Medical University, Xi'an, P. R. China.
Pharmazie. 2021 May 1;76(5):208-214. doi: 10.1691/ph.2021.1363.
Recently we isolated CN-3, a new asterosaponin from starfish , and reported that asterosaponin arrests glioma cell cycle via SCUBE3. However, the multiple mechanisms underlying CN-3 anti-glioma action remains poorly known. Thus, the focus of this study was to evaluate the inhibitory effect of CN-3 on human glioma cells and its underlying molecular mechanisms. U87 and U251 cells were incubated with various concentrations of CN-3, and CCK-8, transmission electron microscopy, ICELLigence, TUNEL, flow cytometry, -acetyl-L-cysteine, and western blot were conducted. As a result, it was found that CN-3 significantly inhibited U87 and U251 cell viability and proliferation in a time- and dose- dependent manner, and also induced mitochondrial apoptosis. Furthermore, we detected that CN-3 downregulated PI3K, P-Akt, AKT and BCL-2, and upregulated cytochrome C and BAX in U87 and U251 cells. Moreover, ROS triggered the inhibition and cell apoptosis for CN-3 via inactivation of P-Akt and activation of cytochrome C. In conclusion, these findings suggest that CN-3 may be a promising candidate for the development of a therapy of glioma.
最近，我们从海星中分离出一种新型的甾族皂甙 CN-3，并报道甾族皂甙通过 SCUBE3 阻止神经胶质瘤细胞周期。然而，CN-3 抗神经胶质瘤作用的多种机制尚不清楚。因此，本研究的重点是评估 CN-3 对人神经胶质瘤细胞的抑制作用及其潜在的分子机制。用不同浓度的 CN-3 孵育 U87 和 U251 细胞，进行 CCK-8、透射电镜、ICELigence、TUNEL、流式细胞术、乙酰-L-半胱氨酸和 Western blot 实验。结果发现，CN-3 可显著抑制 U87 和 U251 细胞活力和增殖，呈时间和剂量依赖性，并诱导线粒体凋亡。此外，我们在 U87 和 U251 细胞中检测到 CN-3 下调了 PI3K、P-Akt、AKT 和 BCL-2，上调了细胞色素 C 和 BAX。此外，ROS 通过失活 P-Akt 和激活细胞色素 C 触发了 CN-3 的抑制和细胞凋亡。综上所述，这些发现表明 CN-3 可能是开发神经胶质瘤治疗方法的有前途的候选药物。
