Ascofuranone inhibits epidermal growth factor-induced cell migration by blocking epithelial-mesenchymal transition in lung cancer cells.

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.

• Authors: Hyo-Weon Kim, Yun-Jeong Jeong, Soon-Kyung Hwang, Yoon-Yub Park, Yung Hyun Choi, Cheorl-Ho Kim, Junji Magae, Young-Chae Chang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 880 Pg. 173199 (Aug 05 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32439259 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• Sesquiterpenes
• Epidermal Growth Factor
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Extracellular Signal-Regulated MAP Kinases
• ascofuranone

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Epidermal Growth Factor (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-myc (metabolism)
• Sesquiterpenes (pharmacology)
• TOR Serine-Threonine Kinases (metabolism)
• Wound Healing (drug effects)