Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University. No. 127 Changle Western Road, 710032 Xi'an, PR China.
Environ Toxicol Pharmacol. 2009 Mar;27(2):264-70. doi: 10.1016/j.etap.2008.11.008. Epub 2008 Nov 25.
Ardipusilloside I, a triterpenoid saponin isolated from Ardisia pusilla A. DC, suppresses the growth of a variety of cancer cells, and has certain immunomodulative properties. Herein, we investigated its effect on glioblastoma cell line U87MG cells and primary cultured human glioblastoma cells, and examined the underlying mechanism of action. Ardipusilloside I substantially decreased the number of viable cells of both cell lines in a time- and concentration-dependent manner, with a similar IC(50) of 4.05μM. Microscopy revealed apoptotic characteristics, including chromatin condensation and cell nucleus fragmentation, demonstrating that ardipusilloside I-induced apoptosis. Ardipusilloside I exposure also gradually increased the sub-G1 fraction (the apoptotic cell population) and an S phase-arrest of both glioblastoma cells. Furthermore, ardipusilloside I increased the expression of Fas and its ligand (FasL), and enhanced the activation of caspase-8 and caspase-3. Additionally, we observed a significant decreased apoptosis after the trigger effection of FasL was abolished by the neutralization antibody anti-FasL antibody and an unchanged apoptosis level when the activation of caspase-8 was interrupted by specific inhibitor z-IETD-fmk, which suggested that a casepase-8 independent FasL/Fas-signaling-mediated death receptor pathway is involved. These data suggested that ardipusilloside I could be developed as a chemotherapeutic agent for the management of gliomas.
从紫金牛属植物 Ardipusilloside I 中分离得到的一种三萜皂苷，可抑制多种癌细胞的生长，并具有一定的免疫调节特性。在此，我们研究了它对神经胶质瘤细胞系 U87MG 细胞和原代培养的人神经胶质瘤细胞的影响，并探讨了其作用机制。Ardipusilloside I 可显著降低两种细胞系中活细胞的数量，呈时间和浓度依赖性，IC50 相似，为 4.05μM。显微镜观察显示凋亡特征，包括染色质浓缩和细胞核碎裂，表明 ardipusilloside I 诱导了细胞凋亡。Ardipusilloside I 暴露还逐渐增加了两种神经胶质瘤细胞的亚 G1 期（凋亡细胞群）和 S 期阻滞。此外，ardipusilloside I 增加了 Fas 及其配体（FasL）的表达，并增强了 caspase-8 和 caspase-3 的激活。此外，我们观察到 FasL 触发效应被中和抗体抗 FasL 抗体阻断后，细胞凋亡明显减少，而 caspase-8 的激活被特异性抑制剂 z-IETD-fmk 阻断后，细胞凋亡水平不变，这表明 FasL/Fas 信号通路通过 caspase-8 非依赖性死亡受体途径参与。这些数据表明，ardipusilloside I 可作为治疗神经胶质瘤的化疗药物进行开发。
