Ascofuranone inhibits epidermal growth factor -induced cell migration by blocking epithelial-mesenchymal transition in lung cancer cells
- Authors
- Kim, HW[Kim, Hyo-Weon]; Jeong, YJ[Jeong, Yun-Jeong]; Hwang, SK[Hwang, Soon-Kyung]; Park, YY[Park, Yoon-Yub]; Choi, YH[Choi, Yung Hyun]; Kim, CH[Kim, Cheorl-Ho]; Magae, J[Magae, Junji]; Chang, YC[Chang, Young-Chae]
- Issue Date
- 5-Aug-2020
- Publisher
- ELSEVIER
- Keywords
- Ascofuranone; c-Myc; Epidermal growth factor; Epithelial-mesenchymal transition; Migration
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, v.880
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF PHARMACOLOGY
- Volume
- 880
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/3579
- DOI
- 10.1016/j.ejphar.2020.173199
- ISSN
- 0014-2999
- Abstract
- 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. © 2020 Elsevier B.V.
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Collections - Science > Department of Biological Science > 1. Journal Articles
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