Chemoprotective epigenetic mechanisms in a colorectal cancer model: Modulation by n-3 PUFA in combination with fermentable fiber

Abstract

Colorectal cancer is the third major cause of cancer-related mortality in both men and women worldwide. The beneficial role of n-3 polyunsaturated fatty acids (PUFA) in preventing colon cancer is substantiated by experimental, epidemiological, and clinical data. From a mechanistic perspective, n-3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely modulates membrane and nuclear receptors, sensors/ion channels, and membrane structure/cytoskeletal function, thereby regulating signaling processes that influence patterns of gene expression and cell phenotype. In addition, n-3 PUFA can synergize with other potential chemoprotective agents known to reprogram the chromatin landscape, such as the fermentable fiber product, butyrate. Nutri-epigenomics is an emerging field of research that is focused on the interaction between nutrition and epigenetics. Epigenetics refers to a group of heterogeneous processes that regulate transcription without changing the DNA coding sequence, ranging from DNA methylation, to histone tail modifications and transcription factor activity. One implication of the nutri-epigenome is that it may be possible to reprogram epigenetic marks that are associated with increased disease risk by nutritional or lifestyle interventions. This review will focus on the nutri-epigenomic role of n-3 PUFA, particularly DHA, as well as the combinatorial effects of n-3 PUFA and fermentable fiber in relation to colon cancer.

Keywords: Fish oil; chemoprevention; colon cancer; docosahexaenoic acid; fermentable fiber; nutri-epigenomics.

Figure 1. Epigenetic effects of n-3 PUFA in the colon

Intestinal genes that are up or down regulated by n-3 PUFA at the mRNA and protein levels. Red font represents gene up-regulation and blue font indicates gene down-regulation. Epigenetic levels of regulation in the nucleus are underlined. Nuclear genes are grouped by classification.