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来自阳春砂根茎的反式-3-甲氧基-5-羟基二氢黄酮(MHS)抑制人肺癌细胞的转移。

trans-3-Methoxy-5-hydroxystilbene (MHS) from the rhizome of Alpinia nantonensis inhibits metastasis in human lung cancer cells.

机构信息

Department of Forestry, National Chung Hsing University, Taichung, Taiwan.

Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.

出版信息

Phytomedicine. 2018 Nov 15;50:223-230. doi: 10.1016/j.phymed.2018.04.010. Epub 2018 Apr 5.

Abstract

BACKGROUND

Alpinia nantoensis (Zingiberaceae) is an aromatic plant endemic to Taiwan, which is used as food flavoring and traditional herbal medicine. The biological activities of compounds isolated from this plant are rarely investigated.

PURPOSE

The present study was aimed to investigate the anti-metastatic potential of trans-3‑methoxy‑5-hydroxystilbene (MHS) a major stilbene isolated from the rhizomes of A. nantonensis.

METHODS

We investigated the anti-metastatic potential of MHS on human non-small cell lung carcinoma (A549) cell line using wound healing, trans-well, western blot, zymography and immunofluorescence assays.

RESULTS

Initial cytotoxicity assay showed that treatment with MHS did not exhibit cytotoxicity to A549 cells up to the concentration of 40 µM. Further in vitro wound healing and transwell chamber assays revealed that MHS significantly inhibited tumor cell migration in a dose-dependent manner, which is associated with inhibition of matrix mettalloprotinase-2 (MMP-2) and matrix mettalloprotinase-9 (MMP-9) at both enzyme and protein levels. The inhibition of MMPs activity by MHS was reasoned by suppression of their corresponding transcription factor, β-catenin as indicated by reduced levels of β-catenin in the nucleus. MHS also regulates epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin and occludin as well as decreasing N-cadherin levels in A549 cells. Furthermore, pre-treatment with MHS significantly inhibited A549 cells migration and EMT in TGF-β induced A549 cells.

CONCLUSION

To the best of our knowledge, this is the first report demonstrating that MHS, a plant-derived stilbene has a promising ability to inhibit lung cancer cell metastasis in vitro.

摘要

背景

益智(姜科)是台湾特有的芳香植物,可用作食品调味剂和传统草药。从这种植物中分离出的化合物的生物活性很少被研究。

目的

本研究旨在研究从益智根茎中分离出的主要二苯乙烯化合物反式-3-甲氧基-5-羟基二苯乙烯(MHS)的抗转移潜力。

方法

我们使用划痕愈合、Transwell、western blot、明胶酶谱和免疫荧光法研究 MHS 对人非小细胞肺癌(A549)细胞系的抗转移潜力。

结果

初始细胞毒性试验表明,MHS 处理在高达 40μM 的浓度下对 A549 细胞没有细胞毒性。进一步的体外划痕愈合和 Transwell 室试验表明,MHS 以剂量依赖的方式显著抑制肿瘤细胞迁移,这与基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的抑制有关,在酶和蛋白水平上均有抑制。MHS 通过抑制其相应的转录因子β-连环蛋白来抑制 MMPs 的活性,这表明核内β-连环蛋白水平降低。MHS 还通过增加 E-钙黏蛋白和闭合蛋白并降低 A549 细胞中的 N-钙黏蛋白水平来调节上皮-间充质转化(EMT)。此外,MHS 的预处理显著抑制 TGF-β诱导的 A549 细胞迁移和 EMT。

结论

据我们所知,这是首次报道表明,植物衍生的二苯乙烯 MHS 具有抑制体外肺癌细胞转移的有前途的能力。

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