Molecular signatures associated with the treatment of triple-negative MDA-MB231 breast cancer cells with the histone deacetylase inhibitors JAHA and SAHA

Librizzi, Mariangela, Caradonna, Fabio, Cruciata, Ilenia, Dębski, Janusz, Supojjanee, Sansook, Dadlez, Michał, Spencer, John and Claudio, Luparello (2017) Molecular signatures associated with the treatment of triple-negative MDA-MB231 breast cancer cells with the histone deacetylase inhibitors JAHA and SAHA. Chemical Research in Toxicology, 30 (12). pp. 2187-2196. ISSN 0893-228X

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Abstract

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of differential display-PCR, proteome analysis and COMET assay techniques and shown some differences in the molecular signature profiles induced by exposure to either HDACis. In particular, in contrast to the more numerous and diversified changes induced by SAHA, JAHA has shown a more selective impact on expression of molecular signatures involved in anti-oxidant activity and DNA repair. Besides expanding the biological knowledge of the effect exerted by the modifications in compound structures on cell phenotype, the molecular elements put in evidence in our study may provide promising targets for therapeutic interventions on TNBCs.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: John Spencer
Date Deposited: 30 Oct 2017 10:03
Last Modified: 19 Jan 2018 14:33
URI: http://sro.sussex.ac.uk/id/eprint/70762

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