Ardipusilloside I induces apoptosis in human glioblastoma cells through a caspase-8-independent FasL/Fas-signaling pathway
Ardipusilloside I induces apoptosis in human glioblastoma cells through a caspase-8-independent FasL/Fas-signaling pathway
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DOI：
10.1016/j.etap.2008.11.008
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发表时间：
2009-03-01
影响因子：
4.3
通讯作者：
Zhang, Xiang
中科院分区：
文献类型：
--
作者：
Xiong, Jian;Cheng, Guang;Zhang, Xiang
Ardipusilloside I是从Ardisia pusilla a . DC中分离出来的三萜皂苷，能抑制多种癌细胞的生长，并具有一定的免疫调节作用。本文研究了其对胶质母细胞瘤细胞系U87MG细胞和原代培养的人胶质母细胞瘤细胞的作用，并探讨了其作用机制。Ardipusilloside I显著降低了两种细胞系的活细胞数量，且呈时间和浓度依赖性，IC50相似，均为4.05 μ M.镜检显示凋亡特征，包括染色质凝集和细胞核断裂，表明Ardipusilloside I诱导了细胞凋亡。Ardipusilloside I暴露也逐渐增加了两种胶质母细胞瘤细胞的亚g1部分（凋亡细胞群）和S期阻滞。此外。心田皂苷I增加了Fas及其配体（FasL）的表达，增强了caspase-8和caspase-3的活化。此外，我们观察到FasL的触发作用被中和抗体anti-FasL抗体消除后，细胞凋亡显著减少，而caspase-8的激活被特异性抑制剂z-lETD-fmk中断后，细胞凋亡水平不变，这表明casepase-8独立的FasL/ fas信号介导的死亡受体途径参与其中。这些数据表明地普西洛苷I可以作为一种治疗胶质瘤的化疗药物。(C) 2008 Elsevier B.V.版权所有
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 IC50 of 4.05 mu M. 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-lETD-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. (C) 2008 Elsevier B.V. All rights reserved.