The Role of Sulforaphane in Epigenetic Mechanisms, Including Interdependence between Histone Modification and DNA Methylation

Abstract

Carcinogenesis as well as cancer progression result from genetic and epigenetic changes of the genome that leads to dysregulation of transcriptional activity of genes. Epigenetic mechanisms in cancer cells comprise (i) post-translation histone modification (i.e., deacetylation and methylation); (ii) DNA global hypomethylation; (iii) promoter hypermethylation of tumour suppressor genes and genes important for cell cycle regulation, cell differentiation and apoptosis; and (iv) posttranscriptional regulation of gene expression by noncoding microRNA. These epigenetic aberrations can be readily reversible and responsive to both synthetic agents and natural components of diet. A source of one of such diet components are cruciferous vegetables, which contain high levels of a number of glucosinolates and deliver, after enzymatic hydrolysis, sulforaphane and other bioactive isothiocyanates, that are involved in effective up-regulation of transcriptional activity of certain genes and also in restoration of active chromatin structure. Thus a consumption of cruciferous vegetables, treated as a source of isothiocyanates, seems to be potentially useful as an effective cancer preventive factor or as a source of nutrients improving efficacy of standard chemotherapies. In this review an attempt is made to elucidate the role of sulforaphane in regulation of gene promoter activity through a direct down-regulation of histone deacetylase activity and alteration of gene promoter methylation in indirect ways, but the sulforaphane influence on non-coding micro-RNA will not be a subject of this review.

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways

“…After transcription, the enzymes Drosha and Dicer process pri-miRNAs and pre-miRNAs to generate mature miRNAs [30] . Sulforaphane, as an effective cancer preventive factor, alters transcriptional activity of genes by histone acetylation and DNA methylation in cancers [31] . Additionally, histone demethylases have been shown to play critical roles in development, differentiation and diseases, such as cancer [32] .…”

MiR-507 inhibits the migration and invasion of human breastcancer cells through Flt-1 suppression

“…Promoter hypermethylation of tumour suppressor genes is a kind of epigenetic mechanisms in cancer cells [22]. Epigenetic modifications have been shown to be crucial mediators underlying in miRNA down-regulation and to display a tight correlation with carcinogenesis [16, 23].…”

The potential role of some phytochemicals in recognition of mitochondrial damage-associated molecular patterns

“…In cytoplasm they could be conjugated to reduced glutathione or cytoplasmic SH-containing proteins (e.g., Keap1). Isothiocyanates were also known as inhibitors of histone deacetylases (Kaufman-Szymczyk et al, 2015) or NFκB (Tortorella et al, 2015), what directly modulate the expression of inflammation-related genes by epigenetic mechanisms.…”