Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells
Lewinska A, Adamczyk-Grochala J, Deregowska A, Wnuk M
Theranostics · 150 citations
Review labels
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How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
Based on full-text disclosure statement.
Publication
- Published
- 2017-01-01 · Theranostics · vol. 7 · issue 14 · pp. 3461–3477
- Publisher
- Ivyspring International Publisher
- Cited
- 189 citations · more than 98% of similar papers · 7.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 80 works
- Access
- Open access (journal) · CC-BY-NC
- Research areas
- Genomics, phytochemicals, and oxidative stress · Epigenetics and DNA Methylation · MicroRNA in disease regulation
- Keywords
- Epigenetics, DNA methylation, Sulforaphane, Cancer research, microRNA, Epigenetic therapy, Cell cycle, Senescence, Cancer, Downregulation and upregulation, Cell cycle checkpoint, Cancer cell, Biology, Chemistry, Cell biology, Gene expression, Biochemistry, Genetics
- MeSH
- humans, isothiocyanates, sulfoxides, protein kinases, micrornas, adenosine triphosphate, anticarcinogenic agents, apoptosis, dna methylation, autophagy, proto-oncogene proteins c-akt, transcriptome, cell cycle checkpoints, mcf-7 cells, dna (cytosine-5-)-methyltransferases, cellular senescence, amp-activated protein kinase kinases
4 authors
From PL
- Anna Lewińska · correspondingUniversity of Rzeszów
- Jagoda Adamczyk‐GrochalaUniversity of Rzeszów
- Anna DeręgowskaMedical University of Warsaw; Postgraduate School of Molecular Medicine; University of Rzeszów
- Maciej WnukUniversity of Rzeszów
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC).
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