Short-chain fatty acids (SCFAs) are ubiquitous lipids produced as a result of bacterial fermentation of dietary fiber. While their role in colorectal cancer is well known, the effect of SCFAs in breast cancer is poorly defined.
To understand the various effects of SCFAs on breast carcinogenesis, we investigated the effect of sodium butyrate (NaB) and sodium propionate (NaP) in MCF-7 cell line.
Materials and methods
Cells were incubated with different concentrations of NaB or NaP for 24, 48, 72 or 96 h. Cell proliferation was assayed using MTT kit. Cell cycle was performed using propidium iodide staining then analyzed with a flow cytometer. Apoptosis was assessed by Hoechst technique and cell-cycle sub-G1 phase.
NaB and NaP inhibited MCF-7 cell proliferation in a dose-dependent manner with respective IC50 of 1.26 mM and 4.5 mM, thus indicating that NaB is more potent than NaP. Low and medium levels of both SCFAs induced morphology changes which are characteristic of a differentiated phenotype. Flow cytometry analysis revealed a blockage in G1 growth phase. Interestingly, removing NaB or NaP from culture media after few days of treatment showed a reversible effect on cell morphology and proliferation where cells reentered the cycle after 24 h of drug wash-out. Finally, treatment with medium levels of these molecules induced low MCF-7 apoptosis, while higher doses led to massive apoptosis.
Our results show that SCFAs may be considered as an interesting inhibitor for breast cancer progression.
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We thank Pr. Hasnaa Bouharoun-Tayoun and Pr. Soulaima Chamat (Lebanese University—Faculty of Public Health Branch 2, Fanar—Lebanon) for allowing us the full access to their laboratory and equipment. This work was supported by a grant from the Lebanese University.
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Electronic supplementary material
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Supplementary file1 Supplementary figure 1: Effect of NaB or NaP on MCF-7 cell line morphology after 24 h of drug wash-out. The upper panel shows the control cell cycle shape in MCF-7 cells. The middle panel shows cell cycle shape after 24 h of 0.5 mM of NaB wash-out. The lower panel shows cell cycle shape after 24 h of 1 mM of NaP wash-out. Supplementary figure 2: Effect of NaB or NaP on MCF-7 cells morphology. The upper panel shows the control cell cycle shape in MCF-7 cells. The middle panel shows the effect of 72 h treatment with 5 mM NaB. The lower panel shows the effect of 72 h treatment with 10 mM of NaP. (PPTX 871 kb)
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Semaan, J., El-Hakim, S., Ibrahim, J. et al. Comparative effect of sodium butyrate and sodium propionate on proliferation, cell cycle and apoptosis in human breast cancer cells MCF-7. Breast Cancer 27, 696–705 (2020). https://doi.org/10.1007/s12282-020-01063-6
- Breast cancer
- Sodium propionate
- Sodium butyrate
- Cell cycle