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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1535563
Sodium butyrate and sodium propionate inhibit breast cancer cell migration and invasion through regulation of epithelial-tomesenchymal transition and suppression of MEK/ERK signaling pathway
Provisionally accepted- 1 Lebanese American University, Beirut, Lebanon
- 2 Lebanese University, Beirut, Lebanon
Objective. This study aims to investigate the roles played by NaB and NaP in breast carcinogenesis by elucidating their potential anti-metastatic effects in the context of tumor migration, invasion, and EMT regulation in two distinct breast cancer cell lines, MCF-7 and MDA-MB-231.Methods. The cytotoxic effect of both compounds on 3D spheroid formation was evaluated using a hanging drop assay. The anti-migratory and anti-invasive potentials of NaB and NaP were investigated through transwell migration and invasion assays. Moreover, their role in regulating epithelial-tomesenchymal transition (EMT) was examined by assessing E-cadherin, vimentin, and β-catenin mRNA and protein expression levels through RT-qPCR and western blot or flow cytometry. β-catenin localization upon treatment was further visualized via immunofluorescence. Protein expression of MEK, p-MEK, ERK, and p-ERK was analyzed by western blot.Our results revealed a dose-and time-dependent impairment of spheroid formation in both cell lines, with NaB exerting a more potent effect than NaP. Both SCFAs were able to significantly inhibit migration and invasion of MDA-MB-231 cells following 24h of treatment. Moreover, treatment with NaB or NaP altered the mRNA and protein profile of EMT-associated markers and abrogated the nuclear translocation of β-catenin. Finally, ERK and MEK phosphorylation was reduced in MDA-MB-231 and MCF-7 cells upon treatment with NaB, and less prominently with NaP.Our study highlights the promising therapeutic potential of NaB and NaP, providing insight into their inhibitory effects on 3D formation, migration, and invasion through EMT regulation and deactivation of MEK/ERK signaling in breast cancer.
Keywords: breast cancer, Short chain fatty acids (SCFAs), Migration, invasion, epithelial-tomesenchymal transition (EMT)
Received: 27 Nov 2024; Accepted: 20 Feb 2025.
Copyright: © 2025 Kharazi, Karam, El Boustany and Ibrahim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jose-Noel Ibrahim, Lebanese American University, Beirut, Lebanon
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