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

International Journal of Molecular Sciences

Agnieszka Kaufman-Szymczyk²  Grzegorz Majewski¹  Katarzyna Lubecka-Pietruszewska²  Krystyna Fabianowska-Majewska² 

[1] Faculty of Public Health, University of Social Sciences in Lodz, 9 Sienkiewicza St., 90-113 Lodz, Poland;Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 6/8 Mazowiecka St., 92-215 Lodz, Poland;

关键词: cruciferous vegetables;    isothiocyanates;    sulforaphane;    epigenetic cancer chemoprevention;   

DOI  :  10.3390/ijms161226195

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.