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Biomolecules 2018, 8(4), 175; https://doi.org/10.3390/biom8040175

Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations

1
Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
2
Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
3
i3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
4
Department of Imuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
5
Institute of Molecular and Cell Biology (IBMC) of the University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
6
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
*
Author to whom correspondence should be addressed.
Received: 22 November 2018 / Revised: 8 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
(This article belongs to the Special Issue Multidrug Combinations)
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Abstract

Cancer is a disease that affects and kills millions of people worldwide. Breast cancer, especially, has a high incidence and mortality, and is challenging to treat. Due to its high impact on the health sector, oncological therapy is the subject of an intense and very expensive research. To improve this therapy and reduce its costs, strategies such as drug repurposing and drug combinations have been extensively studied. Drug repurposing means giving new usefulness to drugs which are approved for the therapy of various diseases, but, in this case, are not approved for cancer therapy. On the other hand, the purpose of combining drugs is that the response that is obtained is more advantageous than the response obtained by the single drugs. Using drugs with potential to be repurposed, combined with 5-fluorouracil, the aim of this project was to investigate whether this combination led to therapeutic benefits, comparing with the isolated drugs. We started with a screening of the most promising drugs, with verapamil and itraconazole being chosen. Several cellular viability studies, cell death and proliferation studies, mainly in MCF-7 cells (Michigan Cancer Foundation-7, human breast adenocarcinoma cells) were performed. Studies were also carried out to understand the effect of the drugs at the level of possible therapeutic resistance, evaluating the epithelial-mesenchymal transition. Combining all the results, the conclusion is that the combination of verapamil and itraconazole with 5-fluorouracil had benefits, mainly by decreasing cell viability and proliferation. Furthermore, the combination of itraconazole and 5-fluorouracil seemed to be the most effective, being an interesting focus in future studies. View Full-Text
Keywords: breast cancer; drug repurposing; drug combinations; 5-fluorouracil; cell viability; epithelial-mesenchymal transition breast cancer; drug repurposing; drug combinations; 5-fluorouracil; cell viability; epithelial-mesenchymal transition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Correia, A.; Silva, D.; Correia, A.; Vilanova, M.; Gärtner, F.; Vale, N. Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations. Biomolecules 2018, 8, 175.

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