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

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posted on 2023-06-08, 22:52 authored by Mariangela Librizzi, Roberto Chiarelli, Liana Bosco, Supojjanee Sansook, Jose M Gascon, John SpencerJohn Spencer, Fabio Caradonna, Claudio Luparello
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Materials

ISSN

1996-1944

Publisher

MDPI

Issue

10

Volume

8

Page range

7041-7047

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-10-22

First Open Access (FOA) Date

2015-10-22

First Compliant Deposit (FCD) Date

2015-10-20

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