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.

Librizzi, M., Chiarelli, R., Bosco, L., Sansook, S., Gascon, J., Spencer, J., et al. (2015). The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells. MATERIALS, 8(10), 7041-7047 [10.3390/ma8105358].

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

LIBRIZZI, Mariangela;CHIARELLI, Roberto;BOSCO, Liana;CARADONNA, Fabio;LUPARELLO, Claudio
2015-01-01

Abstract

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.
2015
Settore BIO/06 - Anatomia Comparata E Citologia
Settore BIO/18 - Genetica
Librizzi, M., Chiarelli, R., Bosco, L., Sansook, S., Gascon, J., Spencer, J., et al. (2015). The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells. MATERIALS, 8(10), 7041-7047 [10.3390/ma8105358].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/148443
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