Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu, 42472, Republic of Korea.
Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 47227, Republic of Korea.
Eur J Pharmacol. 2020 Aug 5;880:173199. doi: 10.1016/j.ejphar.2020.173199. Epub 2020 May 18.
Ascofuranone, an isoprenoid antibiotic initially purified from a culture broth of Ascochyta viciae, has multiple anticancer effects. However, the impacts of ascofuranone on the epithelial-mesenchymal transition (EMT) and epidermal growth factor (EGF)-induced effects on human lung cancer cell lines have not been previously reported. Here, we show that ascofuranone exerts its anticancer effects by inhibiting the EGF-induced EMT and cell migration in human lung cancer cell lines. Ascofuranone significantly inhibited EGF-induced migration and invasion by lung cancer cells, and suppressed EGF-induced morphologic changes by regulating the expression of EMT-associated proteins. In addition, ascofuranone upregulated E-cadherin, and downregulated fibronectin, vimentin, Slug, Snail, and Twist. Inhibition of ERK/AKT/mTOR promoted EGF-induced E-cadherin downregulation and inhibited EGF-induced vimentin upregulation in response to ascofuranone, implying that inhibition of the EGF-induced EMT by ascofuranone was mediated by the ERK and AKT/mTOR pathways. Inhibition of c-Myc suppressed EGF-induced vimentin upregulation, suggesting the involvement of c-Myc. Collectively, these findings suggest that ascofuranone inhibits tumor growth by blocking the EGF-induced EMT through a regulatory mechanism involving ERK, AKT/mTOR, and c-Myc in lung cancer cells.
阿索呋喃酮，一种最初从轮枝镰孢菌发酵液中分离出来的异戊烯抗生素，具有多种抗癌作用。然而，阿索呋喃酮对上皮-间充质转化（EMT）和表皮生长因子（EGF）诱导的人肺癌细胞系的影响尚未见报道。在这里，我们表明阿索呋喃酮通过抑制 EGF 诱导的 EMT 和人肺癌细胞系的细胞迁移来发挥其抗癌作用。阿索呋喃酮显著抑制 EGF 诱导的肺癌细胞迁移和侵袭，并通过调节 EMT 相关蛋白的表达抑制 EGF 诱导的形态变化。此外，阿索呋喃酮上调 E-钙黏蛋白，下调纤连蛋白、波形蛋白、Slug、Snail 和 Twist。ERK/AKT/mTOR 的抑制促进了 EGF 诱导的 E-钙黏蛋白下调，并抑制了 EGF 诱导的波形蛋白上调，这表明阿索呋喃酮通过 ERK 和 AKT/mTOR 途径抑制 EGF 诱导的 EMT。c-Myc 的抑制抑制了 EGF 诱导的波形蛋白上调，表明 c-Myc 的参与。总之，这些发现表明，阿索呋喃酮通过阻断 EGF 诱导的 EMT 来抑制肿瘤生长，这涉及肺癌细胞中的 ERK、AKT/mTOR 和 c-Myc 的调节机制。
