Atorvastatin and Nitrofurantoin Repurposed in the Context of Breast Cancer and Neuroblastoma Cells

Catarina Moura; Ana Salomé Correia; Mariana Pereira; Eduarda Ribeiro; Joana Santos; Nuno Vale

doi:10.3390/biomedicines11030903

Atorvastatin and Nitrofurantoin Repurposed in the Context of Breast Cancer and Neuroblastoma Cells

Biomedicines. 2023 Mar 15;11(3):903. doi: 10.3390/biomedicines11030903.

Authors

Catarina Moura^{1

2

3}, Ana Salomé Correia^{1

2

3}, Mariana Pereira^{1

2

3}, Eduarda Ribeiro^{1

2

3}, Joana Santos^{1

2}, Nuno Vale^{1

2

4}

Affiliations

¹ OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
² CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
³ ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
⁴ Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

Abstract

Chemotherapy still plays a central role in the treatment of cancer. However, it is often accompanied by off-target effects that result in severe side-effects and development of drug resistance. The aim of this work was to study the efficacy of different repurposed drugs on the viability of MCF-7 and SH-SY5Y breast cancer and neuroblastoma cells, respectively. In addition, combinations of these repurposed drugs with a classical chemotherapeutic drug (doxorubicin) were also carried out. The cytotoxic effects of the repurposed drugs were evaluated individually and in combination in both cancer cell lines, assessed by MTT assays and morphological evaluation of the cells. The results demonstrated that atorvastatin reduced the viability of both cell lines. However, nitrofurantoin was able to induce cytotoxic effects in MCF-7 cells, but not in SH-SY5Y cells. The combinations of the repurposed drugs with doxorubicin induced a higher inhibition on cell viability than the repurposed drugs individually. The combination of the two repurposed drugs demonstrated that they potentiate each other. Synergism studies revealed that the combination of doxorubicin with the two repurposed drugs was more effective in SH-SY5Y cells, compared to MCF-7 cells. Taken together, our preliminary study highlights the potential use of atorvastatin and nitrofurantoin in the context of breast cancer and neuroblastoma.

Keywords: MCF-7 cells; SH-SY5Y cells; atorvastatin; doxorubicin; drug combination; drug repurposing; nitrofurantoin.

Grants and funding

This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020—Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia, in the framework of the projects in CINTESIS, R&D Unit (reference UIDB/4255/2020) and within the scope of the project RISE—LA/P/0053/2020. N.V. also acknowledges the support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004 and CHAIR in Onco-Innovation at FMUP.