A1 Journal article – refereed

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

List of Authors: Wawruszak Anna, Luszczki Jarogniew, Halasa Marta, Okon Estera, Landor Sebastian, Sahlgren Cecilia, Rivero-Muller Adolfo, Stepulak Andrzej

Publisher: MDPI

Publication year: 2021

Journal: International Journal of Molecular Sciences

Journal name in source: International journal of molecular sciences

Journal acronym: Int J Mol Sci

Volume number: 22

Issue number: 10

ISSN: 1422-0067

eISSN: 1422-0067

DOI: http://dx.doi.org/10.3390/ijms22105184

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.

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Last updated on 2021-06-08 at 14:50