Abstract Title:

Sulforaphane Alone and in Combination with Clofarabine Epigenetically Regulates the Expression of DNA Methylation-Silenced Tumour Suppressor Genes in Human Breast Cancer Cells.

Abstract Source:

J Nutrigenet Nutrigenomics. 2015 Sep 16 ;8(2):91-101. Epub 2015 Sep 16. PMID: 26372775

Abstract Author(s):

Katarzyna Lubecka-Pietruszewska, Agnieszka Kaufman-Szymczyk, Barbara Stefanska, Barbara Cebula-Obrzut, Piotr Smolewski, Krystyna Fabianowska-Majewska

Article Affiliation:

Katarzyna Lubecka-Pietruszewska

Abstract:

BACKGROUND/AIM: Sporadic breast cancer is frequently associated with aberrant DNA methylation patterns that are reversible and responsive to environmental factors, including diet. In the present study, we investigated the effects of sulforaphane (SFN), a phytochemical from cruciferous vegetables, on the methylation and expression of PTEN and RARbeta2 tumour suppressor genes as well as on the expression of regulators of DNA methylation reaction, DNMT1, p53, and p21, in MCF-7 and MDA-MB-231 human breast cancer cells with different invasive potential. We also evaluate the role of SFN epigenetic effects in support of therapy with clofarabine (ClF) that was recently shown to modulate the epigenome as well.

METHODS: Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis and real-time PCR, respectively.

RESULTS: In both MCF-7 and MDA-MB-231 cells, SFN at IC50 (22 and 46µM, respectively) and a physiologically relevant 10µMconcentration lead to hypomethylation of PTEN and RARbeta2 promoters with concomitant gene up-regulation. The combination of SFN and ClF enhances these effects, resulting in an increase in cell growth arrest and apoptosis at a non-invasive breast cancer stage.

CONCLUSIONS: Our findings provide evidence that SFN activates DNA methylation-silenced tumour suppressor genes in breast cancer cells and may contribute to SFN-mediated support of therapy with an anti-cancer drug, ClF, increasing its applications in solid tumours.

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