期刊
MATERIALS
卷 8, 期 10, 页码 7041-7047出版社
MDPI
DOI: 10.3390/ma8105358
关键词
histone deacetylase inhibitor; extracellular-signal-regulated kinase (ERK); AKT; DNA methyltransferase (DNMT)
类别
资金
- University of Palermo/Italy (FFR)
- Italian Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [PON 01_01059]
- Royal Thai Government
- Engineering and Physical Sciences Research Council [EP/I037229/1] Funding Source: researchfish
- EPSRC [EP/I037229/1] Funding Source: UKRI
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.
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