Abstract C122: The impact of the short-chain fatty acids on viability, motility and migration of oral squamous cell carcinoma cell line

Abstract

Abstract Objectives. Oral squamous cell carcinoma (OSCC) is one of the 10 most common cancers worldwide, with a 5-year relative survival rate of 68%. Since the mechanisms of OSCC in oncogenesis are multifactorial, the development of novel targeted therapies is limited. Short-chain fatty acids (SCFA), i.e. butyrate, acetate, and propionate, are oral microbial products that can potentially inhibit cell growth, proliferation and migration of cancer cells, and may represent an alternative treatment for OSCC as it has not previously evaluated. Here, we measured the impact of SCFA treatment on viability and migration of OSCC cell lines. Methods. OSCC cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum. We performed a cytotoxicity assay with Alamar blue to determine the half-maximal inhibitory concentration (IC50) of the SCFA treatment. Cells were treated with butyrate, acetate, and propionate in concentrations (1:2 dilution factor) starting at 125mM, 500mM, and 125mM, respectively, for 24, 48 and 72 hours. To determine the effects of SCFA on cell migration and motility, we performed a wound-healing assay for 24 hours. OSCC 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 cell culture media with SCFA IC50 determined by our cytotoxicity assay. Results. Cell viability was reduced at higher concentrations for all three SCFAs. Butyrate and propionate did not show an IC50 at 24h. However, butyrate showed an IC 50 at 48h and 72h of 4.4mM and 9.1mM, respectively. Propionate at 48h and 72h showed an IC50 of 1.95 mM and 4.4 mM, respectively. Acetate showed an average IC50 of 261 mM at 24, 48 and 72 hours. In relation to migration, OSCC cell lines treated with butyrate (5nM) show lower motility at 24h when compared to the negative control. In contrast, faster motility was observed when OSCC was treated with acetate (5mM) compared to the negative control. Conclusions. Our results suggest that butyrate reduced oncogenic phenotypes in OSCC while acetate enhanced oncogenic phenotypes. Therefore, SCFAs seem promising alternative in reducing OSCC oncogenic phenotype but require further validation.​ Future work will focus on determining the effects on cell proliferation, migration, and epithelial-mesenchymal transition. Citation Format: Ariana S Garcia, Liah Marie Roman Calderon, Angel Amaral, Jeannette Salgado, Gabriel Borges, Esther Peterson, Josue Perez. The impact of the short-chain fatty acids on viability, motility and migration of oral squamous cell carcinoma cell line [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C122.