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

Abstract

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.

<p>Nanomedicine-based formulations containing &omega;-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases</p>

“…In our opinion, this topic deserves particular attention, particularly by the researchers who have been studying for decades the beneficial effects of ω-3 PUFAs in the prevention of CVD and cancer. 1,39,57,62,96,98,117 Even though this issue cannot be tackled exhaustively in just one paragraph, it is essential to outline some considerations.…”

“…We have studied the antineoplastic potential of ω-3 PUFAs in CRC and melanoma for many years [96][97][98][99][100][101] and investigated the possible mechanisms underlying the beneficial action of these fatty acids. We have recently developed new SLNs for the delivery of ω-3 PUFAs to C32 melanoma cells 91 and HT-29 and HCT116 CRC cells, 92 to reduce possible ω-3 PUFA oxidative degradation of these compounds, and, thus, prolong their shelf-life, enhance their bioavailability, and improve their antineoplastic activity ( Table 5; Figure 3B and C).…”

ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies

“…However, growing epidemiological, experimental, and clinical evidence showing the beneficial effects of ω3 PUFA in several stages of CRC management represent a solid rationale for their exploitation in therapeutic combinatory strategies (28). The antineoplastic effects of ω3 PUFA have been studied for many years, and multiple biological mechanisms have been suggested to explain their inhibitory effects on cancer cell growth (29, 30). However, in recent years, growing attention has been given to the antineoplastic activity of ω3 PUFA related to the action of these bioactive molecules on inflammatory process, due to the pathogenic role of inflammation in the development of many kinds of tumors.…”

“…More recently, the epigenetic regulation of gene expression and the polarization of macrophages toward pro-resolving M2 phenotype have emerged as novel mechanisms explaining the antineoplastic effects of ω3 PUFA at the colon level, although additional studies are needed for a deeper comprehension of this issue (30). Finally, the capacity of ω3 PUFA to modulate inflammatory pathways and to generate lipid mediators critical for the resolution of inflammation (e.g., resolvins, protectins, and maresins) has gained attention as a main mechanism involved in the beneficial effects of ω3 PUFA against CRC (66).…”

Ficolin‐A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis

“…Intestinal macrophages are important tissue immune cells that are ideally situated at the interface with the enteric luminal environment to respond to microbes and other potential stimuli . Macrophages play a crucial role in the pathogenesis of IBD.…”