Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines – An Isobolographic AnalysisReport as inadecuate




Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines – An Isobolographic Analysis - Download this document for free, or read online. Document in PDF available to download.

Histone deacetylase inhibitors HDIs are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid VPA and suberoylanilide hydroxamic acid SAHA, vorinostat, alone or in combination with cisplatin CDDP on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive antagonistic interaction was observed for the combination of CDDP with VPA in MDA-MB-231 -triple-negative- i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs-CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.



Author: Anna Wawruszak , Jarogniew J. Luszczki, Aneta Grabarska, Ewelina Gumbarewicz, Magdalena Dmoszynska-Graniczka, Krzysztof Polberg,

Source: http://plos.srce.hr/



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