Characterization of the Pro-Inflammatory Cytokine IL-1β on Butyrate Oxidation in Colorectal Cancer Cells.

Cancer, in part, is driven, by alterations in cellular metabolism that promote cell survival and cell proliferation. Identifying factors that influence this shift in cellular metabolism in cancer cells is important. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that has been reported to be elevated in colorectal cancer patients. While much is known toward the effect of dietary nutrients on regulating inflammation and the inflammatory response, which includes cytokines such as IL-1β, far less is understood how cytokines impact nutrient fate to alter cancer cell metabolism. Butyrate, a nutrient derived from the fermentation of dietary fiber in the colon, is the preferential exogenous energetic substrate used by non-cancerous colonocytes, but is used less efficiently by colorectal cancer cells. To test whether IL-1β alters colonocyte energy metabolism, we measured butyrate oxidation in HCT116 colorectal cancer cells with and without IL-1β. We hypothesize that IL-1β will push cancerous colonocytes away from the utilization and oxidation of butyrate. In this study, we demonstrate that pretreatment of colorectal cancer cells with IL-1β diminished butyrate oxidation and NADH levels. This effect was blocked with the interleukin receptor antagonist A (IL-1RA). Moreover, IL-1β suppressed basal mitochondrial respiration and lowered the mitochondrial spare capacity. By using inhibitors to block downstream targets of the interleukin-1 receptor pathway, we show that p38 is required for the IL-1β-mediated decrease in butyrate oxidation. These data provide insight into the metabolic effects induced by IL-1β in colorectal cancer, and identify relevant targets that may be exploited to block the effects of this cytokine. J. Cell. Biochem. 118: 1614-1621, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Citation

Megan Johnstone, Natalie Bennett, Cynthia Standifer, Alexis Smith, Anna Han, Ahmed Bettaieb, Jay Whelan, Dallas R Donohoe. Characterization of the Pro-Inflammatory Cytokine IL-1β on Butyrate Oxidation in Colorectal Cancer Cells. Journal of cellular biochemistry. 2017 Jun;118(6):1614-1621

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PMID: 27922186

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