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Inhibition of tumor migration and invasion by fenofibrate via suppressing epithelial-mesenchymal transition in breast cancers.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Feb; Vol. 483, pp. 116818. Date of Electronic Publication: 2024 Jan 11. - Publication Year :
- 2024
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Abstract
- The recurrence and metastasis in breast cancer within 3 years after the chemotherapies or surgery leads to poor prognosis with approximately 1-year overall survival. Large-scale scanning research studies have shown that taking lipid-lowering drugs may assist to reduce the risk of death from many cancers, since cholesterol in lipid rafts are essential for maintain integral membrane structure and functional signaling regulation. In this study, we examined five lipid-lowering drugs: swertiamarin, gemfibrozil, clofibrate, bezafibrate, and fenofibrate in triple-negative breast cancer, which is the most migration-prone subtype. Using human and murine triple-negative breast cancer cell lines (Hs 578 t and 4 T1), we found that fenofibrate displays the highest potential in inhibiting the colony formation, wound healing, and transwell migration. We further discovered that fenofibrate reduces the activity of pro-metastatic enzymes, matrix metalloproteinases (MMP)-9 and MMP-2. In addition, epithelial markers including E-cadherin and Zonula occludens-1 are increased, whereas mesenchymal markers including Snail, Twist and α-smooth muscle actin are attenuated. Furthermore, we found that fenofibrate downregulates ubiquitin-dependent GDF-15 degradation, which leads to enhanced GDF-15 expression that inhibits cell migration. Besides, nuclear translocation of FOXO1 is also upregulated by fenofibrate, which may responsible for GDF-15 expression. In summary, fenofibrate with anti-cancer ability hinders TNBC from migration and invasion, and may be beneficial to repurposing use of fenofibrate.<br />Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.<br /> (Copyright © 2023. Published by Elsevier Inc.)
- Subjects :
- Animals
Humans
Mice
Growth Differentiation Factor 15 pharmacology
Growth Differentiation Factor 15 therapeutic use
Cell Line, Tumor
Cell Movement
Hypolipidemic Agents pharmacology
Hypolipidemic Agents therapeutic use
Epithelial-Mesenchymal Transition
Lipids
Cell Proliferation
Triple Negative Breast Neoplasms metabolism
Fenofibrate pharmacology
Fenofibrate therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 483
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38215994
- Full Text :
- https://doi.org/10.1016/j.taap.2024.116818