HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates
Rajendran P, Kidane AI, Yu TW, Dashwood WM, Bisson WH, Löhr CV, Ho E, Williams DE, Dashwood RH
Epigenetics · 95 citas
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Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Células o muestras de laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Gobierno
- National Cancer Institute
- Gobierno
- National Institute of Environmental Health Sciences
- Gobierno
- NCI NIH HHS
- Gobierno
- NIEHS NIH HHS
- Subvenciones
- National Cancer Institute (R01 CA-122906); National Cancer Institute (CA-80176); National Institute of Environmental Health Sciences (ES-00-210); National Cancer Institute (R29 CA065525); National Cancer Institute (CA 090890); National Institute of Environmental Health Sciences (P30ES000210); National Cancer Institute (CA-65525); National Cancer Institute (R01 CA080176); National Cancer Institute (R01 CA065525); National Cancer Institute (P01 CA090890); National Cancer Institute (R01 CA122959); National Cancer Institute (CA122959); National Cancer Institute (CA122906)
Según 5 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2013-06-01 · Epigenetics · vol. 8 · número 6 · págs. 612–623
- Editorial
- Landes Bioscience
- Citado
- 120 citas · más que el 97% de estudios similares · 6.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 49 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · Histone Deacetylase Inhibitors Research · Epigenetics and DNA Methylation
- Palabras clave
- DNA damage, Biology, Acetylation, Histone, Cancer research, Proteostasis, DNA repair, Histone Acetyltransferases, Cancer cell, Cell biology, Biochemistry, Cancer, DNA, Genetics
- MeSH
- colon, cell line, cell line, tumor, humans, colonic neoplasms, dna damage, isothiocyanates, sulfoxides, histone deacetylases, endodeoxyribonucleases, carrier proteins, nuclear proteins, antineoplastic agents, apoptosis, gene expression, acetylation, autophagy, histone deacetylase inhibitors, cell cycle checkpoints
9 autores
- Praveen Rajendran🇺🇸🇳🇴 · autor de correspondenciaOregon State University; Oregon University System; Corvallis Environmental Center; Linus (Norway)
- Ariam I. Kidane🇺🇸🇳🇴Oregon State University; Oregon University System; Corvallis Environmental Center; Linus (Norway)
- Tianwei Yu🇺🇸🇳🇴Oregon State University; Oregon University System; Corvallis Environmental Center; Linus (Norway)
- Wan‐Mohaiza Dashwood🇺🇸🇳🇴Oregon State University; Oregon University System; Corvallis Environmental Center; Linus (Norway)
- William H. Bisson🇺🇸Oregon State University; Corvallis Environmental Center
- Christiane V. Löhr🇺🇸Oregon State University; Corvallis Environmental Center
- Emily H. Ho🇺🇸🇳🇴Oregon State University; Corvallis Environmental Center; Linus (Norway)
- David E. J. Williams🇺🇸🇳🇴Oregon State University; Corvallis Environmental Center; Linus (Norway)
- Roderick H. Dashwood🇺🇸🇳🇴Oregon State University; Corvallis Environmental Center; Linus (Norway)
Resumen
El texto original del estudio, en el idioma en que se publicó.
Histone deacetylases (HDACs) and acetyltransferases have important roles in the regulation of protein acetylation, chromatin dynamics and the DNA damage response. Here, we show in human colon cancer cells that dietary isothiocyanates (ITCs) inhibit HDAC activity and increase HDAC protein turnover with the potency proportional to alkyl chain length, i.e., AITC < sulforaphane (SFN) < 6-SFN < 9-SFN. Molecular docking studies provided insights into the interactions of ITC metabolites with HDAC3, implicating the allosteric site between HDAC3 and its co-repressor. ITCs induced DNA double-strand breaks and enhanced the phosphorylation of histone H2AX, ataxia telangiectasia and Rad3-related protein (ATR) and checkpoint kinase-2 (CHK2). Depending on the ITC and treatment conditions, phenotypic outcomes included cell growth arrest, autophagy and apoptosis. Coincident with the loss of HDAC3 and HDAC6, as well as SIRT6, ITCs enhanced the acetylation and subsequent degradation of critical repair proteins, such as CtIP, and this was recapitulated in HDAC knockdown experiments. Importantly, colon cancer cells were far more susceptible than non-cancer cells to ITC-induced DNA damage, which persisted in the former case but was scarcely detectable in non-cancer colonic epithelial cells under the same conditions. Future studies will address the mechanistic basis for dietary ITCs preferentially exploiting HDAC turnover mechanisms and faulty DNA repair pathways in colon cancer cells vs. normal cells.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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