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RESEARCH PRODUCT
The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells
John SpencerJose Miguel GasconSupojjanee SansookClaudio LuparelloRoberto ChiarelliFabio CaradonnaMariangela LibrizziLiana Boscosubject
DNA methyltransferase (DNMT)medicine.drug_classDNA methyltransferaselcsh:TechnologymedicineGeneral Materials ScienceCancer epigeneticsSettore BIO/06 - Anatomia Comparata E Citologialcsh:Microscopyhistone deacetylase inhibitorlcsh:QC120-168.85QD0415Histone deacetylase 5lcsh:QH201-278.5extracellular-signal-regulated kinase (ERK)ChemistryHistone deacetylase 2lcsh:TCommunicationAKTHistone deacetylase inhibitorMolecular biologySettore BIO/18 - Geneticalcsh:TA1-2040DNA methylationDNMT1lcsh:Descriptive and experimental mechanicslcsh:Electrical engineering. Electronics. Nuclear engineeringlcsh:Engineering (General). Civil engineering (General)lcsh:TK1-9971DNA hypomethylationQD0241description
The histone deacetylase inhibitor N-1-(ferrocenyl)-N-8-hydroxyoctanediamide (JAHA) down-regulates extracellular-signal-regulated kinase (ERK) and its activated form in triple-negative MDA-MB231 breast cancer cells after 18 h and up to 30 h of treatment, and to a lesser extent AKT and phospho-AKT after 30 h and up to 48 h of treatment. Also, DNA methyltransferase 1 (DNMT1), 3b and, to a lesser extent, 3a, downstream ERK targets, were down-regulated already at 18 h with an increase up to 48 h of exposure. Methylation-sensitive restriction arbitrarily-primed (MeSAP) polymerase chain reaction (PCR) analysis confirmed the ability of JAHA to induce genome-wide DNA hypomethylation at 48 h of exposure. Collective data suggest that JAHA, by down-regulating phospho-ERK, impairs DNMT1 and 3b expression and ultimately DNA methylation extent, which may be related to its cytotoxic effect on this cancer cytotype.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-10-01 |