Epigenetic Events Associated with Breast Cancer and Their Prevention by Dietary Components Targeting the Epigenome

Abstract

Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in reversing some of these defects. Methylation of CpG islands is an important component of the epigenetic code, and a number of genes become abnormally methylated in breast cancer patients. Currently, several epigenetic-based synthetic drugs that can reduce DNA hypermethylation and histone deacetylation are undergoing preclinical and clinical trials. However, these chemicals are generally very toxic and do not have gene specificity. Epidemiological studies have shown that Asian women are less prone to breast cancer due to their high consumption of soy food than the Caucasian women of western countries. Moreover, complementary/and or alternative medicines are commonly used by Asian populations which are rich in bioactive ingredients known to be chemopreventive against tumorigenesis in general. Examples of such agents include dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, isothiocyanates from plant foods, curcumin from turmeric, resveratrol from grapes, and sulforaphane from cruciferous vegetables. These bioactive components are able to modulate epigenetic events, and their epigenetic targets are known to be associated with breast cancer prevention and therapy. This approach could facilitate the discovery and development of novel drugs for the treatment of breast cancer. In this brief review, we will summarize the epigenetic events associated with breast cancer and the potential of some of these bioactive dietary components to modulate these events and thus afford new therapeutic or preventive approaches.

Laccaic Acid A Is a Direct, DNA-competitive Inhibitor of DNA Methyltransferase 1

“…Nucleoside demethylating agents, such as 5-azadC, are used in the treatment of myelodysplastic syndrome and acute myeloid leukemia (15,46). Particularly at high doses, these compounds act non-specifically on the genome, causing the activation of many genes and potentially transposons, which can lead to genomic instability (47,48). Furthermore, 5-azaC is incorporated into RNA and induces off-target effects (16).…”

Modulation of Epigenetic Targets for Anticancer Therapy: Clinicopathological Relevance, Structural Data and Drug Discovery Perspectives

“…Of particular interest is the elucidation of the polypharmacological behavior of dietary and nutraceutical components. Indeed, many clinical, physiopathological and epidemiological studies highlighted the detrimental or beneficial role of nutritional factors in conjunction to epigenetic alterations [27,37,66,91,238,593].…”

Epigenetic Diabetic Vascular Complications

“…Inhibition of p65 acetylation-dependent NF-kB activation can occur by epigallocatechin-3-gallate, a strong HAT inhibitor; which could be considered potentially to inhibit the development of diabetic retinopathy (60). Regarding the effect of environmental and dietary factors on epigenetic modifications, many natural compounds have been found to have beneficial effects (61,62). Resveratrol, a natural extract of red grapes, is involved in the adjustment of histone deacetylases (63).…”