Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and β-catenin signaling pathways
Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and β-catenin signaling pathways
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DOI：
10.1016/j.bmcl.2016.07.004
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发表时间：
2016-08-15
影响因子：
2.7
通讯作者：
Lee, Sang Yeol
中科院分区：
文献类型：
--
作者：
Jung, Okkeun;Lee, Jongsung;Lee, Sang Yeol
天麻皂苷AIII （TAIII）是一种从天麻中分离得到的甾体皂苷类化合物。众所周知，它可以通过抗炎作用改善学习和记忆缺陷。TAIII也被报道在HeLa癌细胞中诱导线粒体介导的细胞凋亡之前的自噬，抑制人类结直肠癌细胞的生长，因此被认为是一种潜在的抗癌药物。在这项研究中，我们验证了TAIII在A549人非小细胞肺癌（NSCLC）细胞中的诱导凋亡和细胞周期阻滞作用。随后，我们报道了TAIII抑制A549人NSCLC细胞的迁移和侵袭。我们提出，两种基质金属蛋白酶（MMPs）， MMP-2和MMP-9，众所周知参与癌症转移，被TAIII治疗减弱。TAIII通过抑制ERK1/2、Src/FAK和β -catenin信号通路发挥对MMP-2和MMP-9的抑制作用，这些信号通路与MMP-2和MMP-9的调控密切相关。(C) 2016 Elsevier Ltd.版权所有。
Timosaponin AIII (TAIII) is a type of steroidal saponins isolated from Anemarrhena asphodeloides. It was known to improve learning and memory deficits through anti-inflammatory effects. TAIII was also reported to induce autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells and inhibit the growth of human colorectal cancer cells, thus regarded as a potential candidate for anti-cancer agent. In this study, we verified apoptosis-inducing and cell-cycle-arresting effects of TAIII in A549 human non-small-cell lung cancer (NSCLC) cells. Then, we report that TAIII suppresses migration and invasion of A549 human NSCLC cells. We propose that two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, which are well known to be involved in cancer-metastasis, are attenuated by the treatment of TAIII. TAIII exerts its suppressive effects on MMP-2 and MMP-9 via inhibitions of ERK1/2, Src/FAK and beta-catenin signalings which are closely related with the regulations of MMP-2 and MMP-9. (C) 2016 Elsevier Ltd. All rights reserved.