Enterolactone induces apoptosis in human prostate carcinoma LNCaP cells via a mitochondrial-mediated, caspase-dependent pathway
Enterolactone induces apoptosis in human prostate carcinoma LNCaP cells via a mitochondrial-mediated, caspase-dependent pathway
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DOI：
10.1158/1535-7163.mct-07-0220
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发表时间：
2007-09-01
影响因子：
5.7
通讯作者：
Lin, Xu
中科院分区：
文献类型：
--
作者：
Chen, Li-Hua;Fang, Jing;Lin, Xu
哺乳动物木脂素肠内酯是植物木脂素的主要代谢产物，已显示其抑制前列腺癌的生长和发展。然而，关于其抗癌活性的机制基础知之甚少。在这项研究中，我们报告说，肠内酯选择性抑制LNCaP前列腺癌细胞的生长，触发凋亡。机制研究表明，肠内酯诱导的细胞凋亡的特点是剂量依赖性的线粒体膜电位的损失，细胞色素c的释放和切割的procaspase-3和聚（ADP-核糖）-聚合酶（PARP）的半胱天冬酶依赖性的泛半胱天冬酶抑制剂z-VAD-favorite减弱肠内酯介导的细胞凋亡的能力。机制研究表明Akt、GSK-3 β、MDM 2和p53在肠内酯依赖性细胞凋亡中的作用。我们的研究结果鼓励进一步研究肠内酯作为一个有前途的化学预防剂对前列腺癌。
The mammalian lignan enterolactone is a major metabolite of plant-based lignans that has been shown to inhibit the growth and development of prostate cancer. However, little is known about the mechanistic basis for its anticancer activity. In this study, we report that enterolactone selectively suppresses the growth of LNCaP prostate cancer cells by triggering apoptosis. Mechanistic studies showed that enterolactone-induced apoptosis was characterized by a dose-dependent loss of mitochondrial membrane potential, release of cytochrome c and cleavage of procaspase-3 and poly(ADP-ribose)-polymerase (PARP) Caspase dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate enterolactone-mediated apoptosis. Mechanistic studies suggested roles for Akt, GSK-3 beta, MDM2, and p53 in enterolactone-dependent apoptosis. Our findings encourage further studies of enterolactone as a promising chemopreventive agent against prostate cancer.