The histone deacetylase inhibitor JAHA down-regulates pERK and global DNA methylation in MDA-MB231 breast cancer cells

Librizzi, Mariangela, Chiarelli, Roberto, Bosco, Liana, Sansook, Supojjanee, Gascon, Jose M, Spencer, John, Caradonna, Fabio and Luparello, Claudio (2015) The histone deacetylase inhibitor JAHA down-regulates pERK and global DNA methylation in MDA-MB231 breast cancer cells. Materials, 8 (10). pp. 7041-7047. ISSN 1996-1944

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Abstract

The histone deacetylase inhibitor N1-(ferrocenyl)-N8-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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: John Spencer
Date Deposited: 22 Oct 2015 11:29
Last Modified: 07 Mar 2017 10:20
URI: http://sro.sussex.ac.uk/id/eprint/57260

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