Theranostics 2017; 7(14):3461-3477. doi:10.7150/thno.20657 This issue Cite

Research Paper

Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells

Anna Lewinska1✉, Jagoda Adamczyk-Grochala1, Anna Deregowska2, 3, Maciej Wnuk2

1. Laboratory of Cell Biology, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland;
2. Department of Genetics, University of Rzeszow, Kolbuszowa, Poland;
3. Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.

Citation:
Lewinska A, Adamczyk-Grochala J, Deregowska A, Wnuk M. Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells. Theranostics 2017; 7(14):3461-3477. doi:10.7150/thno.20657. https://www.thno.org/v07p3461.htm
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Abstract

Graphic abstract

Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced. The effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling. Moreover, SFN stimulated energy stress as judged by decreased pools of ATP and AMPK activation, and autophagy induction. Anticancer effects of SFN were mediated by global DNA hypomethylation, decreased levels of DNA methyltransferases (DNMT1, DNMT3B) and diminished pools of N6-methyladenosine (m6A) RNA methylation. SFN (10 µM) also affected microRNA profiles, namely SFN caused upregulation of sixty microRNAs and downregulation of thirty two microRNAs, and SFN promoted statistically significant decrease in the levels of miR-23b, miR-92b, miR-381 and miR-382 in three breast cancer cells. Taken together, we show for the first time that SFN is an epigenetic modulator in breast cancer cells that results in cell cycle arrest and senescence, and SFN may be considered to be used in epigenome-focused anticancer therapy.

Keywords: sulforaphane, breast cancer cells, DNA methylation, microRNA.


Citation styles

APA
Lewinska, A., Adamczyk-Grochala, J., Deregowska, A., Wnuk, M. (2017). Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells. Theranostics, 7(14), 3461-3477. https://doi.org/10.7150/thno.20657.

ACS
Lewinska, A.; Adamczyk-Grochala, J.; Deregowska, A.; Wnuk, M. Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells. Theranostics 2017, 7 (14), 3461-3477. DOI: 10.7150/thno.20657.

NLM
Lewinska A, Adamczyk-Grochala J, Deregowska A, Wnuk M. Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells. Theranostics 2017; 7(14):3461-3477. doi:10.7150/thno.20657. https://www.thno.org/v07p3461.htm

CSE
Lewinska A, Adamczyk-Grochala J, Deregowska A, Wnuk M. 2017. Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells. Theranostics. 7(14):3461-3477.

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