Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells
Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells
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DOI：
10.1016/j.ejphar.2007.07.028
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发表时间：
2007-11-28
影响因子：
5
通讯作者：
Kuo, Po-Lin
中科院分区：
文献类型：
--
作者：
Chen, Chung-Yi;Hsu, Ya-Ling;Kuo, Po-Lin
本研究首次研究了从桂叶中分离的异黄酮类化合物异黄酮A（IKA），其在人非小细胞肺癌A549细胞中表现出抗增殖活性。结果表明，IKA通过阻滞细胞周期进程于G 0/G1期并诱导细胞凋亡来抑制A549的增殖。细胞周期阻滞与p21/wAFI水平升高和细胞周期蛋白D1、细胞周期蛋白E、Cdk 2、Cdk 4和Cdk 6以p53介导的方式减少有关。IKA处理还增加了p53磷酸化（Ser 15）并降低了p53-MDM 2的相互作用。IKA处理触发了线粒体凋亡途径，通过改变Bcl-2比率、细胞色素c释放和半胱天冬酶-9活化来指示。caspase-9抑制剂预处理可抑制IKA诱导的A549细胞凋亡，提示caspase-9的激活参与了IKA诱导的A549细胞凋亡。我们的研究首次报道了IKA对人非小细胞肺癌细胞的抗增殖活性可能与p53/p21的诱导和线粒体凋亡系统的启动有关。(c)2007年由Elsevier B.V出版
This study is the first to investigate isokotomolide A (IKA), a butanolide compound isolated from the leaves of Cinnamomum kotoense Kanehira & Sasaki (Lauraceaee), which exhibits an anti-proliferative activity in human non-small cell lung cancer A549 cells. The results show that IKA inhibits the proliferation of A549 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Blockade of cell cycle was associated with increased p21/wAFI levels and reduced amounts of cyclin D1, cyclin E, Cdk2, Cdk4, and Cdk6 in a p53-mediated manner. IKA treatment also increased p53 phosphorylation (Ser15) and decreased the interaction of p53-MDM2. IKA treatment triggered the mitochondrial apoptotic pathway, indicated by changing BaxBcl-2 ratios, cytochrome c release and caspase-9 activation. In addition, pretreatment of cells with caspase-9 inhibitor inhibited IKA-induced apoptosis, indicating that caspase-9 activation was involved in A549 cells' apoptosis induced by IKA. Our study reports here for the first time that the induction of p53/p21 and the initiation of the mitochondrial apoptotic system may participate in the anti-proliferative activity of IKA in human non-small cell lung cancer cells. (c) 2007 Published by Elsevier B.V