Pro‐inflammatory Cytokine, IL‐1B, Diminishes Butyrate Oxidation in Colorectal Cancer Cells

Most colorectal cancers undergo the Warburg effect. This shifts cell energetics toward increased glycolytic metabolism and away from oxidative metabolism and butyrate oxidation. Butyrate, derived from the fermentation of dietary fiber, is the preferred energetic substrate of the non‐cancerous colonocyte. Butyrate, at physiologically relevant levels in the colon, inhibits histone deacetylases to regulate gene expression and subsequently increase apoptosis in colorectal cancer cells. Accordingly, we sought to determine the effects of the pro‐inflammatory cytokine interleukin‐1 β (IL‐1β) on butyrate oxidation in real‐time cellular respiration using a Seahorse Analyzer. We utilized 2 colorectal cancer cell lines (HCT116 and HT‐29) in these studies. Cells were placed in fatty acid oxidation buffer supplemented with or without IL‐1B (1ng/mL) treatment for one hour prior to Seahorse assay. Butyrate and 2‐deoxyglucose (2DG) were injected into wells.. Baseline measurements reveal injected butyrate (final concentration 5mM) to significantly increase oxidative consumption rate (OCR) as compared to control (p<0.05, n=5). Concurrently, cells injected with butyrate and treated with IL‐1B showed significantly increased OCR as compared to control (p<0.05, n=5); yet significantly decreased butyrate oxidation as compared to butyrate injected wells (p <0.05, n=5). Upon injection of 2DG (final concentration 5mM), which blocks glucose oxidation leaving only butyrate as the sole energetic substrate, only butyrate‐treated cells showed significant increases in OCR (p<0.0, n=5). Thus, IL‐1β appears to diminish butyrate oxidation in colorectal cancer cells, which may affect subsequent genomic acetylation and all downstream targets including proliferation and apoptotic pathways.