Alantolactone induces activation of apoptosis in human hepatoma cells
Alantolactone induces activation of apoptosis in human hepatoma cells
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土木香内酯诱导人肝癌细胞凋亡激活
DOI：
10.1016/j.fct.2012.06.014
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发表时间：
2012-09-01
影响因子：
4.3
通讯作者：
Zou, Guo-Lin
中科院分区：
文献类型：
--
作者：
Lei, Jia-Chuan;Yu, Jian-Qing;Zou, Guo-Lin
木香内酯是一种倍半萜内酯，具有抗炎作用。在这项研究中，我们提供的证据表明，它可以被开发为一种新的药物对人类肝癌。我们观察到土木香内酯对人肝癌细胞系HepG 2、Bel-7402和SMMC-7721细胞的作用导致细胞生长的剂量依赖性抑制。我们选择HepG 2细胞系作为测试模型系统。木香内酯处理的HepG 2细胞导致剂量依赖性的诱导凋亡和细胞阻滞在G2-M期。这种凋亡诱导似乎是通过调节Bcl-2家族蛋白水平和激活caspase介导的。此外，caspase-8和Bid激活，线粒体跨膜电位的丧失和细胞色素c的释放表明死亡受体和线粒体之间存在串扰！路径。我们还观察到土木香内酯处理细胞导致NF-κ B/p65的剂量依赖性降低。此外，在alantolactone处理的细胞中，观察到p53蛋白水平的显著和进行性增加。综上所述，我们的数据表明，土木香内酯可以开发作为一种药物对人类肝癌。(C)2012爱思唯尔有限公司保留所有权利。
Alantolactone, a sesquiterpene lactone, possesses anti-inflammatory property. In this study, we provide evidence that it could be developed as a novel agent against human liver cancer. We observed that alantolactone treatment to HepG2, Bel-7402 and SMMC-7721 cells, human liver cancer cell lines resulted in a dose-dependent inhibition of cell growth. We selected HepG2 cell line as a test model system. Alantolactone treatment of HepG2 cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via modulating the protein levels of Bcl-2 family and activation of caspases. Moreover, caspase-8 and Bid activation, loss of mitochondrial transmembrane potential and cytochrome c release suggest the existence of a cross-talk between the death receptor and the mitochondria! pathways. We also observed that alantolactone treatment of cells resulted in a dose-dependent decrease in NF- kappa B/p65. In addition, a significant and progressive increase in the level of p53 protein in alantolactone-treated cells was observed. Taken together, our data suggest that alantolactone could be developed as an agent against human liver cancer. (C) 2012 Elsevier Ltd. All rights reserved.