Investigational New Drugs

, Volume 36, Issue 5, pp 782–796 | Cite as

Pre-clinical effects of metformin and aspirin on the cell lines of different breast cancer subtypes

  • Maria Eduarda Azambuja Amaral
  • Laura Roesler Nery
  • Carlos Eduardo Leite
  • Walter Filgueira de Azevedo Junior
  • Maria Martha CamposEmail author


Background Breast cancer is highly prevalent among women worldwide. It is classified into three main subtypes: estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+), and triple negative breast cancer (TNBC). This study has evaluated the effects of aspirin and metformin, isolated or in a combination, in breast cancer cells of the different subtypes. Methods The breast cancer cell lines MCF-7, MDA-MB-231, and SK-BR-3 were treated with aspirin and/or metformin (0.01 mM - 10 mM); functional in vitro assays were performed. The interactions with the estrogen receptors (ER) were evaluated in silico. Results Metformin (2.5, 5 and 10 mM) altered the morphology and reduced the viability and migration of the ER+ cell line MCF-7, whereas aspirin triggered this effect only at 10 mM. A synergistic effect for the combination of metformin and aspirin (2.5, 5 or 10 mM each) was observed in the TNBC cell subtype MDA-MB-231, according to the evaluation of its viability and colony formation. Partial inhibitory effects were observed for either of the drugs in the HER2+ cell subtype SK-BR-3. The effects of metformin and aspirin partly relied on cyclooxygenase-2 (COX-2) upregulation, without the production of lipoxins. In silico, metformin and aspirin bound to the ERα receptor with the same energy. Conclusion We have provided novel evidence on the mechanisms of action of aspirin and metformin in breast cancer cells, showing favorable outcomes for these drugs in the ER+ and TNBC subtypes.


Breast cance Drug repurposing Metformin Aspirin 



We would like to thank Dr. Eduardo Filippi-Chiela for providing the MCF-7 cell line and Dr. Mônica Ryff Moreira Roca Vianna for sharing the laboratory facilities for the western blotting analyzes.


This study was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil. MEAA is a master’s degree student in Cellular and Molecular Biology supported by the CAPES/PROEX Program. M.M.C. and W.F.A received grants from CNPq (Grant Numbers: 303842–2014-8 and 308883–2014-4, respectively).

Compliance with ethical standards

Conflict of interest

None of the authors have any conflict of interest to disclose regarding the publication of the present manuscript.

Ethical approval

This article has not featured any studies with human participants or animals whilst it was being performed by any of the authors.

Supplementary material

10637_2018_568_MOESM1_ESM.docx (11.9 mb)
ESM 1 (DOCX 12225 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Maria Eduarda Azambuja Amaral
    • 1
    • 2
  • Laura Roesler Nery
    • 3
  • Carlos Eduardo Leite
    • 2
  • Walter Filgueira de Azevedo Junior
    • 1
    • 4
  • Maria Martha Campos
    • 1
    • 2
    • 5
    Email author
  1. 1.Programa de Pós-Graduação em Biologia Celular e Molecular, Escola de CiênciasPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  2. 2.Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da SaúdePontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  3. 3.ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Escola de CiênciasPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  4. 4.Laboratório de Biologia de Sistemas Computacionais, Escola de CiênciasPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  5. 5.Programa de Pós-Graduação em Odontologia, Escola de Ciências da SaúdePontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil

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