Effect of red meat metabolites and nutrient deprivation on gene expression of HCT116 colorectal cancer cells

Metabolic adaptation allows cancer cells to survive and thrive in changing (nutritional) environments and is therefore a major contributor to cancer progression. The role of diet herein remains largely unexplored. Red and processed meat consumption is associated to colorectal cancer (CRC), e.g. by the influence of metabolites in the colon lumen. In this study, the impact of individual and mixtures of meat-derived metabolites on cancer cell metabolic adaptations upon nutritional deprivation is investigated. Using respirometry and transcriptomics, shifts in the ratio of oxidative and glycolytic metabolism were demonstrated upon treatment with hemin (HEM) and kynurenine (KYN). In addition, we found that a combination of HEM and KYN had the strongest impact on the metabolic adaptability during glucose deprivation, potentially supported by stimulated intracellular lipid storage. These results reveal an important role of red meat metabolites in cancer cell bioenergetics by acting on key metabolic pathways and show combined effects of HEM and KYN.