The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells

Materials

Mariangela Librizzi¹  Roberto Chiarelli¹  Liana Bosco¹  Supojjanee Sansook²  Jose M. Gascon²  John Spencer²  Fabio Caradonna¹  Claudio Luparello¹ 

[1] Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Edificio 16, Università di Palermo, Viale delle Scienze, Palermo 90128, Italy;Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK;

关键词: histone deacetylase inhibitor;    extracellular-signal-regulated kinase (ERK);    AKT;    DNA methyltransferase (DNMT);   

DOI  :  10.3390/ma8105358

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.