ArticleCellular oncology (Dordrecht, Netherlands)2020
Ascofuranone suppresses invasion and F-actin cytoskeleton organization in cancer cells by inhibiting the mTOR complex 1 signaling pathway.
Article in Cellular oncology (Dordrecht, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- The PI3K-AKT-mTOR signaling pathway mediates epithelial mesenchymal transition and cytoskeletal architecture changes induce to renal fibrosis after Bisphenol S exposure.Scientific reports · 2025Article
- SSPH I, A Novel Anti-cancer Saponin, Inhibits EMT and Invasion and Migration of NSCLC by Suppressing MAPK/ERK1/2 and PI3K/AKT/ mTOR Signaling Pathways.Recent patents on anti-cancer drug discovery · 2024Article
- Amino Acid Derivatives of Ginsenoside AD-2 Induce HepG2 Cell Apoptosis by Affecting the Cytoskeleton.Molecules (Basel, Switzerland) · 2023Article
- Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis.Antimicrobial agents and chemotherapy · 2023Article
- Three-dimensional migration of human amniotic fluid stem cells involves mesenchymal and amoeboid modes and is regulated by mTORC1.Stem cells (Dayton, Ohio) · 2021Article
- Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products.Molecules (Basel, Switzerland) · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeAscofuranone is an antiviral antibiotic that is known to exert multiple anti-tumor effects, including cell cycle arrest, inhibition of mitochondrial respiration, and inhibition of angiogenesis. In this study, we investigated the molecular mechanisms underlying the anti-metastatic effects of ascofuranone in insulin-like growth factor-I (IGF-1)-responsive cancer cells.
methodsThe inhibitory effect of ascofuranone on cancer cell migration and invasion was assessed using scratch wound healing and Matrigel invasion assays, respectively. F-actin cytoskeleton organization was assessed using FITC conjugated phalloidin staining. Target gene expression was evaluated using Western blotting and gene silencing was performed using siRNA transfections. Finally, the anti-metastatic effect of ascofuranone was investigated in vivo.
resultsWe found that ascofuranone suppressed IGF-1-induced cell migration, invasion and motility in multiple cancer cell lines. The effects of ascofuranone on actin cytoskeleton organization were found to be mediated by suppression of the mTOR/p70S6K/4EBP1 pathway. Ascofuranone inhibited IGF-1-induced mTOR phosphorylation and actin cytoskeleton organization via upregulation of AMPK and downregulation of Akt phosphorylation. It also selectively suppressed the IGF-1-induced mTOR complex (mTORC)1 by phosphorylation of Raptor, but did not affect mTORC2. Furthermore, we found that focal adhesion kinase (FAK) activation decreased in response to ascofuranone, rapamycin, compound C and wortmannin treatment. Finally, we found that ascofuranone suppressed phosphorylation of FAK and mTOR and dephosphorylation of Raptor in cancerous metastatic lung tissues in vivo.
conclusionsOur data indicate that ascofuranone suppresses IGF-1-induced cancer cell migration and invasion by blocking actin cytoskeleton organization and FAK activation through inhibition of the mTORC1 pathway, and reveal a novel anti-metastatic function of this compound.
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