Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L.) Millsp.] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway
Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L.) Millsp.] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway
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DOI：
10.1016/j.cbi.2010.07.009
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发表时间：
2010-10-06
影响因子：
5.1
通讯作者：
Efferth, Thomas
中科院分区：
文献类型：
--
作者：
Luo, Meng;Liu, Xia;Efferth, Thomas
Cajanol (5-羟基-3-(4-羟基-2-甲氧基苯基)-7-甲氧基苯并二氢吡喃-4-酮) 是一种来自木豆 [Cajanus cajan (L) Millsp.] 根的异黄烷酮。作为木豆中最有效的植物抗毒素，木豆酚对癌细胞的细胞毒活性尚未见报道。在本研究中，研究了木豆酚对 MCF-7 人乳腺癌细胞的抗癌活性。为了探讨木豆酚抑制细胞生长的潜在机制、细胞周期分布、DNA碎片测定和核变化的形态学评估。 ROS 生成、线粒体膜电位 (Delta Psi m) 破坏以及 caspase-3 和 caspase-9、Bax 的表达。 Bcl-2。在 MCF-7 细胞中测量 PARP 和细胞色素 c。 Cajanol 以时间和剂量依赖性方式抑制 MCF-7 细胞的生长。处理72小时后IC50值为54.05μM，处理48小时后IC50值为58.32μM； 24小时后为83.42μM。 Cajanol 将细胞周期阻滞在 G2/M 期，并通过 ROS 介导的线粒体依赖性途径诱导细胞凋亡。 Western blot分析显示，木豆酚抑制Bcl-2表达并诱导Bax表达，从而破坏线粒体外膜并导致细胞色素c释放。线粒体细胞色素 c 的释放与 caspase-9 和 caspase-3 级联的激活有关，并且活性 caspase-3 参与 PARP 裂解。所有这些信号转导途径都参与启动细胞凋亡。据我们所知，这是第一份在体外证明木豆酚对癌细胞具有细胞毒活性的报告。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) is an isoflavanone from Pigeonpea [Cajanus cajan (L) Millsp.] roots. As the most effective phytoalexin in pigeonpea, the cytotoxic activity of cajanol towards cancer cells has not been report as yet. In the present study, the anticancer activity of cajanol towards MCF-7 human breast cancer cells was investigated. In order to explore the underlying mechanism of cell growth inhibition of cajanol, cell cycle distribution, DNA fragmentation assay and morphological assessment of nuclear change. ROS generation, mitochondrial membrane potential (Delta Psi m) disruption, and expression of caspase-3 and caspase-9, Bax. Bcl-2. PARP and cytochrome c were measured in MCF-7 cells. Cajanol inhibited the growth of MCF-7 cells in a time and dose-dependent manner. The IC50 value was 54.05 mu M after 72 h treatment, 58.32 mu M after 48 h; and 83.42 mu M after 24h. Cajanol arrested the cell cycle in the G2/M phase and induced apoptosis via a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that cajanol inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage. All of these signal transduction pathways are involved in initiating apoptosis. To the best of our knowledge, this is the first report demonstrating the cytotoxic activity of cajanol towards cancer cells in vitro. (C) 2010 Elsevier Ireland Ltd. All rights reserved.