Targeting the Epigenome as a Novel Therapeutic Approach for Breast Cancer

Abstract

Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to undergo hypermethylation at promoter region in breast cancer. In addition, histone deacetylases (HDACs) contribute to transcriptional repression by removing acetyl group at lysine residues leading to tumorigenesis. Since epigenetic changes are reversible, therapeutic approaches have been applied with epigenetic modification drugs such as DNMT inhibitors and HDAC inhibitors. In this chapter, we will summarize the feature of epigenetic markers in breast cancer cells and the effect of single or combination of epigenetic reagents for breast cancer therapy.

Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations

“…Dietary intervention is a promising strategy to reverse dysregulation of epigenetic modifications that are associated with tumorigenesis [21]. The anticancer effect of bioactive compounds such as phytochemicals are mediated by epigenetic regulations such as inhibiting DNA methyltransferases (DNMTs), inhibiting histone deacetylase (HDACs), and modulating microRNA [22].…”

Astragaloside IV promotes cardiac remodeling after myocardial infarction by inhibiting DNMT3B-mediated Runx3 methylation via downregulating LncRNA MIRT1 expression

“…Moreover, echocardiographic examinations were performed to determine the effect of AS-IV on cardiac function. FS and EF were significantly lower in MI Runx3 to undergo hypermethylation in the promoter region of breast cancer (Oh et al, 2017). We found that MIRT1 could bind Suz12 protein, enabling Suz12 to recruit DNMT3B in the Runx3 promoter region to promote Runx3 methylation and downregulate Runx3 expression.…”

Sesamol Epigenetically Induces Estrogen Receptor α Re-expression by Upregulating miR-370-3p in Estrogen Receptor α-Negative Breast Cancer

“…Studies have shown that DNA methylation plays a role in certain pathological events including breast carcinoma . In addition, certain tumor suppressors were attenuated because of aberrant promoter DNA methylation in the process of breast carcinoma genesis and progression …”

“…10 In addition, certain tumor suppressors were attenuated because of aberrant promoter DNA methylation in the process of breast carcinoma genesis and progression. 11 Sesamol, a naturally occurring phenolic water-soluble compound, is usually extracted from sesame seeds and sesame oil. More importantly, it is one of the most active constituents in sesame oil and thought to be responsible for the therapeutic effects of sesame oil.…”