Short-Chain Fatty Acids Induce Cell Death in Glioblastoma Cells via Distinct Mechanisms ^†

Introduction: Glioblastoma (GBM) is the most common and aggressive type of glioma. Although current treatment strategies are well-established, their effectiveness remains limited. Recent studies have highlighted the potential of short-chain fatty acids (SCFAs)—such as acetate, butyrate, propionate, and valeric acid—as therapeutic agents against various solid tumors. Methodology: We evaluated the cell viability of A172, a GBM cell line, upon treatment with SCFAs using MTT assay. We then investigated the underlying molecular mechanisms of cell death induced by sodium butyrate and valeric acid, using their respective IC50 concentrations via Real-Time qPCR. Results: The IC50 values indicated that A172 cells were more sensitive to sodium butyrate and valeric acid (IC50 = 9.22 mM and 19.04 mM, respectively) than to sodium propionate and sodium acetate (IC50 = 41.21 mM and 121.2 mM, respectively) after 72 h of treatment. In cells treated with sodium butyrate, we observed an increased expression of BAK and decreased expression of P53 and CASP1. Treatment with valeric acid led to upregulation of BCL-2, BAK, and RIPK3, along with downregulation of P53. Conclusions: Our preliminary findings suggest that SCFAs, particularly sodium butyrate and valeric acid, can induce cell death in GBM cells through distinct molecular pathways. While further studies are necessary to elucidate the exact mechanisms, these results support the potential of SCFAs as therapeutic candidates for glioblastoma.