Abstract B039: Butyrate and propionate-reduced oncogenic phenotypes in triple-negative breast cancer
Authors: Román-Calderón Liah M , García-López Ariana S , Salgado-Montilla Jeannette L , Borges-Vélez Gabriel , Peterson-Peguero Esther A , Pérez-Santiago Josué 
Published: February 2024

Abstract
Objectives Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer affecting 5% of all patients with no known treatment. Hispanic women show a higher risk of developing this type of cancer at an early age. Heterogeneity of TNBC between patients makes it challenging to devolop a effective treatment. The compostion of microbiome amongst the patients has a high variablity that could affect the production of the microbial products. The changes in microbial products have not been previously evaluated and could possibly contribute to chronic inflammation in the patients. Short-chain fatty acids (SCFA), i.e. butyrate, acetate, and propionate which are metabolical products of the microbiome that can potentially inhibit cell growth, proliferation and migration of cancer cells, may represent an alternative treatment for TNBC. Here, we measured the impact of SCFAs treament on viability and migration of MDA-231 cell lines. Methods MDA-231 cell line is an aggressive triple-negative breast cancer (TNBC) cell line common for evaluating new therapeutic strategies. MDA-231 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum and we evaluated oncogenic phenotypes (cell viability and migration) after SCFA treatment. Cells were treated with butyrate, acetate, and propionate in cell culture media at seven concentrations starting at 125mM (1:2 dilution factor) for 24, 48 and 72 hours (h). We determined the cell viability using Alamar blue and determined the half-maximal inhibitory concentration (IC50) after SCFA treatment at all time points. Furthermore, we performed a wound-healing assay for 24h to evaluate the impact of SCFA on cell migration. MDA-231 cells were cultured to a 100% confluency and a scratch was performed in the cell monolayer to create an artificial gap, simulating the wound. Immediately after performing the wound, the cells were treated with SCFA at concentrations of 1mM and 5mM. Results Higher concentrations of butyrate and propionate reduced cell viability for MDA-231 was reduced. Particularly, butyrate showed an IC50 at 24h, 48h and 72h of 4.7mM, 4.34 mM and 3.6mM, respectively. However, propionate showed an IC50 only at 48h and 72h of 21.09 mM and 19.5 mM, respectively. There was no impact in cell viability after acetate treatment. In relation to migration, MDA-231 cell lines treated with butyrate and propionate at 5mM show a slower migration rate at 24h when compared to the untreated cells. Conclusions Our results suggest that butyrate and propionate can reduce oncogenic phenotypes in MDA-231. Future work will measure the impact of SCFA on cell proliferation, motility, and epithelial-mesenchymal transition. SCFAs may represent a promising target for novel treatment strategies for TNCB.
Citation Format: Liah M Román-Calderón, Ariana S García-López, Jeannette L Salgado-Montilla, Gabriel Borges-Vélez, Esther A Peterson-Peguero, Josué Pérez-Santiago. Butyrate and propionate-reduced oncogenic phenotypes in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B039.