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 citas
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- Financiación independiente
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Publicación
- Publicado
- 2017-01-01 · Theranostics · vol. 7 · número 14 · págs. 3461–3477
- Editorial
- Ivyspring International Publisher
- Citado
- 189 citas · más que el 98% de estudios similares · 7.4× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 80 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY-NC
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Epigenetics and DNA Methylation · MicroRNA in disease regulation
- Palabras clave
- 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 autores
- Anna Lewińska🇵🇱 · autor de correspondenciaUniversity of Rzeszów
- Jagoda Adamczyk‐Grochala🇵🇱University of Rzeszów
- Anna Deręgowska🇵🇱Medical University of Warsaw; Postgraduate School of Molecular Medicine; University of Rzeszów
- Maciej Wnuk🇵🇱University of Rzeszów
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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