Cancer cell metabolism, epigenetics and the potential influence of dietary components – A perspective

Cancer cells are characterized by alterations in cell metabolism including increased glucose consumption and aerobic glycolysis, commonly known as the “Warburg effect”. Underlying mechanisms for this metabolic switch have been associated with genetic defects in pathways regulating metabolic processes. Recent research indicates that epigenetic alterations, e.g. in DNA methylation of promoter regions of glycolytic enzymes, might contribute to the deregulated expression of enzymes involved in cell metabolism. Alternatively, changes in cell metabolism could alter the availability of co-factors for epigenetic processes. This perspective will summarize current knowledge on interactions between cancer cell metabolism and epigenetic modulation of gene regulation, and how both processes can be affected by dietary components. Natural compounds with reported mechanisms targeting cancer cell metabolism include folate, flavonoids, green tea polyphenols, genistein from soy, silymarin from milk thistle, and the anthraquinone derivative shikonin. Reversible acetylation of histones and non-histone proteins has been shown to affect cell metabolism and other cellular processes, and can be targeted by inhibitors of histone deacetylases (HDACs) and histone acetyl transferases (HATs). Natural compounds with HDAC or HAT inhibitory activity include butyrate, sulforaphane from broccoli, diallyldisulfide (DADS) from garlic, cambinol and dihydrocoumarin, diindolylmethane, epigallocatechin gallate (EGCG), curcumin, anacardic acid and garcinol. Currently we can only speculate whether their influence on epigenetic mechanisms is of importance for normalization of the deregulated cancer cell metabolism. It can be anticipated that the emergence of sensitive metabonomics technologies and genome-wide detection of epigenetic alterations in DNA methylation, histone modifications, and miRNA expression, will improve our understanding of the relationship between epigenetics and cancer cell metabolism.