Ko Hyeonseok, Jeon Hyelin, Lee Dahae, Choi Hyo-Kyoung, Kang Ki Sung, Choi Kyung-Chul
Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea; Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, South Korea.
Bioorg Med Chem Lett. 2015 Dec 1;25(23):5508-13. doi: 10.1016/j.bmcl.2015.10.067. Epub 2015 Oct 23.
In the epithelial-mesenchymal transition (EMT), an important cellular process, epithelial cells become mesenchymal cells. This process is also critically involved in cancer metastasis. Sanguiin H6 is a compound derived from ellagitannin, which is found in berries. Sanguiin H6 shows various pharmacological properties, including anti-angiogenic activity. Because the possible role of sanguiin H6 in the EMT and the underlying molecular mechanisms are unclear, we investigated the effect of sanguiin H6 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT and promotes lung adenocarcinoma migration and invasion through the Smad2/3 signaling pathway. Thus, to understand the inhibitory effects of sanguiin H6 on lung cancer migration and invasion, we investigated the ability of sanguiin H6 to inhibit TGF-β1-induced EMT in the A549 cell line. We found that sanguiin H6 significantly prevented the activation of Smad2/3 signaling pathway by TGF-β1. Additionally, sanguiin H6 increased the expression of the epithelial marker E-cadherin and repressed the expression of Snail and the mesenchymal marker N-cadherin during TGF-β1-induced EMT. Moreover, sanguiin H6 regulated the expression of EMT-dependent genes induced by TGF-β1. Finally, sanguiin H6 inhibited the migration and invasion of TGF-β1-stimulated A549 cells. Taken together, our findings provide new evidence that sanguiin H6 suppresses lung cancer migration and invasion in vitro by inhibiting TGF-β1 induction of the EMT.
在上皮-间质转化（EMT）这一重要的细胞过程中，上皮细胞会转变为间质细胞。该过程在癌症转移中也起着关键作用。桑根苷H6是一种源自鞣花单宁的化合物，存在于浆果中。桑根苷H6具有多种药理特性，包括抗血管生成活性。由于桑根苷H6在EMT中的潜在作用及其分子机制尚不清楚，我们研究了桑根苷H6对EMT的影响。转化生长因子-β1（TGF-β1）可诱导EMT，并通过Smad2/3信号通路促进肺腺癌的迁移和侵袭。因此，为了了解桑根苷H6对肺癌迁移和侵袭的抑制作用，我们研究了桑根苷H6在A549细胞系中抑制TGF-β1诱导的EMT的能力。我们发现，桑根苷H6可显著阻止TGF-β1对Smad2/3信号通路的激活。此外，在TGF-β1诱导的EMT过程中，桑根苷H6增加了上皮标志物E-钙黏蛋白的表达，并抑制了Snail和间质标志物N-钙黏蛋白的表达。而且，桑根苷H6调节了TGF-β1诱导的EMT相关基因的表达。最后，桑根苷H6抑制了TGF-β1刺激的A549细胞的迁移和侵袭。综上所述，我们的研究结果提供了新的证据，表明桑根苷H6通过抑制TGF-β1诱导的EMT在体外抑制肺癌的迁移和侵袭。
