Epigenetic regulation of gene expression and M2 macrophage polarization as new potential omega-3 polyunsaturated fatty acid targets in colon inflammation and cancer.

INTRODUCTION: It has become increasingly clear that dietary habits may affect the risk/progression of chronic diseases with a pathogenic inflammatory component, such as colorectal cancer. Considerable attention has been directed toward the ability of nutritional agents to target key molecular pathways involved in these inflammatory-related diseases. AREAS COVERED: ω-3 Polyunsaturated fatty acids (PUFA) and their oxidative metabolites have attracted considerable interest as possible anti-inflammatory and anti-cancer agents, especially in areas such as the large bowel, where the influence of orally introduced substances is high and tumors show deranged PUFA patterns. On this basis, we have analyzed pre-clinical findings that have recently revealed new insight into the molecular pathways targeted by ω-3 PUFA. EXPERT OPINION: The findings analyzed herein demonstrate that ω-3 PUFA may exert beneficial effects by targeting the epigenetic regulation of gene expression and altering M2 macrophage polarization during the inflammatory response. These mechanisms need to be better explored in the large bowel, and further studies could better clarify their role and the potential of dietary interventions with ω-3 PUFA in the large bowel. The epigenomic mechanism is discussed in view of the potential of ω-3 PUFA to enhance the efficacy of other agents used in the therapy of colorectal cancer.