The natural compound codonolactone attenuates TGF-β1-mediated epithelial-to-mesenchymal transition and motility of breast cancer cells
The natural compound codonolactone attenuates TGF-β1-mediated epithelial-to-mesenchymal transition and motility of breast cancer cells
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天然化合物 codonolactone 减弱 TGF-β1 介导的上皮间质转化和乳腺癌细胞的运动性
DOI：
10.3892/or.2015.4394
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发表时间：
2016-01-01
期刊：
影响因子：
4.2
通讯作者：
Lu, Hong
中科院分区：
文献类型：
--
作者：
Fu, Jianjiang;Ke, Xiaoqin;Lu, Hong
苍术内酯（Codonolactone， CLT）是苍术的天然产物，是苍术的主要生物活性成分，也存在于一系列其他草药中，如党参、凤尾草和苍术。这种倍半萜内酯已被证明具有一系列的活性，包括抗过敏活性，抗炎，抗癌，胃保护和神经保护活性。在此之前，我们发现CLT在体内和体外都具有显著的抗转移特性。为了确定emt参与的机制是否有助于CLT的抗转移作用，我们检查了CLT的抗emt特性及其潜在机制。本研究在体外和体内证明了CLT抑制tgf - β 1诱导的上皮-间质转化（EMT）。此外，tgf - β信号的下调与CLT的抗emt特性有关。western blotting数据显示，在乳腺癌细胞中，tgf - β 1刺激Runx2的激活，而CLT阻断Runx2的激活。最后，为了验证CLT诱导的EMT抑制是否导致转移潜能的抑制，我们确定了CLT对细胞侵袭和迁移的影响。发现tgf - β 1诱导的迁移和侵袭在MDA-MB-231和MDA-MB-468细胞中均被CLT显著阻断。总之，我们的研究结果表明，CLT在体外和体内抑制EMT的编程，从而抑制转移性乳腺癌细胞的运动。CLT的抑制作用是由于它能够抑制tgf - β信号传导和Runx2磷酸化。
Codonolactone (CLT), a natural product, is the major bioactive component of Atractylodes lancea, and also found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes macrocephala Koidz. This sesquiterpene lactone has been demonstrated to exhibit a range of activities, including anti-allergic activity, anti-inflammatory, anticancer, gastroprotective and neuroprotective activity. Previously, we found that CLT showed significant anti-metastatic properties in vitro and in vivo. In order to determine whether EMT-involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-EMT properties of CLT and its potential mechanisms. Here it was demonstrated that CLT inhibited TGF-beta 1-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, downregulation of TGF-beta signaling was associated with the anti-EMT properties of CLT. Data from western blotting showed that, in breast cancer cells, TGF-beta 1 stimulated the activation of Runx2, and CLT blocked the activation of Runx2. Finally, to verify whether CLT-induced EMT inhibition leads to suppression of metastatic potential, the effects of CLT on cell invasion and migration were determined. It was found that TGF-beta 1-induced migration and invasion was significantly blocked by CLT in both MDA-MB-231 and MDA-MB-468 cells. Collectively, our findings demonstrated that CLT inhibited programming of EMT in vitro and in vivo, resulting in inhibition of motility of metastatic breast cancer cells. The inhibitory effect of CLT was due to its ability to inhibit TGF-beta signaling and Runx2 phosphorylation.