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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271991 | GEO | 2026/05/27

REPOSITORIES: GEO

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Project description:It has been proposed that endogenously formed N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as one of the critical factors in the formation of endogenous NOCs, it is of high importance to replace or reduce the nitrite levels in meat. Therefore, the PHYTOME project was initiated (Phytochemicals to reduce nitrite in meat products; www.phytome.eu), an EU funded research project aiming to develop innovative meat products in which the food additive sodium nitrite (E251) has been replaced by natural compounds originating from fruits and vegetables. A human dietary intervention study was conducted in which healthy subjects consumed 300 grams of meat for two weeks, in subsequent order: normal processed red meat, white meat, and red processed meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of standard-nitrite PHYTOME meat products leads to a significant reduction in Apparent Total N-nitroso Compounds (ATNC) levels in faecal water, a surrogate marker of endogenously formed NOCs, as compared to the consumption of conventional processed red meat products. A reduction of nitrite in the PHYTOME meat lowered these levels even further. In addition, DNA strand breaks induced in ex-vivo faecal water exposed Caco-2 cells and O6-methyl-guanine adducts levels in colonic DNA were significantly higher after consumption of normal processed red meat as compared to white meat intake. PHYTOME meat intake resulted in reduced levels of these genotoxic markers, however, these were not statistically significant. Whole genome gene expression analyses in colonic tissue identified differentially expressed genes and genes associated with ATNC, which are related to molecular pathways which may explain cancer risk initiation after intake of processed red meat and cancer risk prevention after intake of the PHYTOME meat. Together these results indicate that addition of natural extracts to conventional processed red meat products results in reduced endogenous formation of NOCs, and may therefore contribute to a reduced risk of CRC, which is mechanistically supported by gene expression analyses.

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

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