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

ABSTRACT

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.

KEYWORDS:

• Cancer
• colon
• epigenetics
• inflammation
• macrophage polarization
• omega-3 PUFA

Article highlights

• Dietary ω-3 long chain polyunsaturated fatty acids (ω-3 PUFA) and their oxidative metabolites were shown to have the potential to inhibit inflammation and modulate tumor cell proliferation and survival.

• Colorectal (CR) mucosa is particularly subject to the influence of the regulatory action of dietary ω-3 PUFA, and increased levels of ω-6 PUFA and ω-6/ω-3 PUFA ratio were recently demonstrated in the cancerous tissues of CR cancer patients.

• These fatty acids were shown to have pleiotropic effects and the possible mechanisms/molecular targets involved are under intensive investigation.

• This review focuses on the two mechanisms recently involved in the beneficial effects exerted by ω-3 PUFA at colon level: (a) ω-3 PUFA modulation of the epigenetic regulation of genes involved in cell growth and inflammatory response; (b) ω-3 PUFA (or their metabolites) as inducers of the pro-resolving M2 macrophage phenotype in the inflamed tissues.

• Additional information on the potential role of ω-3 PUFA as epigenomic regulators could be useful in hypothesizing new therapeutic and preventive approaches which combine antineoplastic drugs/agents and these fatty acids.

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Financial & competing interests disclosure

The authors were supported in part by grants awarded to G Calviello by Università Cattolica del S. Cuore, Rome, Italy (Linea D.3.2 2013 and Linea D1 2013). This funding was awarded under the university’s program for the promotion and diffusion of scientific research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.