The Effect of Sodium Butyrate on the Cell Viability of Triple-Negative Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, accounting for 2-4% of cases but contributing to approximately 10% of annual breast cancer mortality in the USA. Studies have shown that the molecular profile of IBC differs significantly from other subtypes, however, these changes do not fully account for its aggressive and rapid metastasis. The microbiome, consisting of a diverse community of microorganisms living in the human body, has emerged as an influential player in cancer development and progression of different cancers, including breast cancer. There is evidence suggesting that microbial metabolites, such as short-chain fatty acids (SCFA), contribute to immune response, tumor growth, and the efficacy of chemotherapeutic drugs and immune checkpoint inhibitors. Additionally, the therapeutic potential of butyrate, an SCFA, in treating different cancers through the activation of MAPK pathways and apoptosis is well characterized, but its use in the treatment of IBC has not been assessed. In this study, we treated SUM149 ((Triple Negative IBC)  cells with multiple concentrations of butyrate at different time points and evaluated them in the context of MAPK activation, proliferation, and apoptosis. SUM149 cells were treated with 0, 3.12, 6.25, 12.50, 25, and 50mM concentrations of Sodium Butyrate for 1, 3, 6, and 24h. MAPK activation was assessed through western blot using specific antibodies including anti- p-JNK, p-p38, p38, P-ERK1/2, and ERK1/2 and normalized with anti-GAPDH as a loading control. Proliferating and apoptotic cells were detected by fluorescence microscopy of KI67-FITC and Annexin V-Cy3 respectively. We observed a dose-dependent increase in activation of p-JNK at 1h, while no difference was observed at longer time points. We saw a decrease in cell proliferation and an increase in cell apoptosis in SUM149 cells treated with 6.25mM of butyrate after 24h. Additionally, while we didn’t see a significant decrease in cell proliferation we did see a significant increase in apoptosis in cells treated with 50mM of butyrate after 24h. We are currently examining the molecular mechanisms involved in the effects of butyrate on cell viability in TNIBC-SUM149. Butyrate’s regulation of the JNK MAPK pathway may play an important role in the viability of TN-IBC cells treated with butyrate. These findings could establish a mechanistic link between the MAPK pathway and the effects of butyrate on TN-IBC cell viability.