Epigenetic Mechanisms Underlying Diet-Sourced Compounds in the Prevention and Treatment of Gastrointestinal Cancer

Rebecca      W. Knackstedt; Vondina      R. Moseley; Michael      J. Wargovich

doi:10.2174/187152012803833053

Abstract

The development of colon cancer, the third most diagnosed cancer and third leading cause of cancer deaths in the United States, can be influenced by genetic predispositions and environmental exposures. As 80% of colon cancer cases are sporadic in nature, much interest lies in determining risk factors that may foster its development, as well as identifying compounds that could inhibit colon cancer development or halt progression. A major risk factor for sporadic colon cancer is a high fat, Western diet which has been linked to a cancer-prone, pro-inflammatory state. Cultures which place an emphasis on fresh fruits and vegetables demonstrate lower colon cancer incidences. Diet not only has the potential to encourage colon cancer development, but recent evidence demonstrates that certain dietary natural products can halt colon cancer development and progression via epigenetic regulation. Epigenetic dysregulation may contribute to inflammation-driven diseases, such as cancer, and can lead to the inappropriate silencing of genes necessary to inhibit cancer development. Natural compounds have shown the ability to reverse epigenetic dysregulation in in vitro and in vivo models. As current allopathic medicines aimed at reversing epigenetic silencing are accompanied with the risk of toxicity and side effects, much interest lies in being able to harness the disease preventing properties in natural products. Here, we discuss the epidemiology of colon cancer, describe the need for natural approaches to inhibit disease development and highlight natural products which have been shown to inhibit gastrointestinal cancer initiation and progression in vitro or in vivo through epigenetic modulation.

Keywords: Cancer, Cancer Prevention, Colon, Colon cancer, Colon Cancer Prevention, Diet, Dietary Intervention, Disease Modification, DNA Methyltransferases, Epigenetics, Epigenetic Dysregulation, Gene Silencing, Histone Deacetylase, Inflammation, Natural Products