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Journal of Cancer Research and Clinical Oncology

, Volume 142, Issue 10, pp 2119–2130 | Cite as

11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes

  • Lauana Greicy Tonon Lemos
  • Gabriela Nestal de Moraes
  • Deborah Delbue
  • Flavia da Cunha Vasconcelos
  • Paula Sabbo Bernardo
  • Eric W–F. Lam
  • Camilla Djenne Buarque
  • Paulo Ribeiro Costa
  • Raquel Ciuvalschi MaiaEmail author
Original Article – Cancer Research

Abstract

Multidrug resistance is the major obstacle for successful treatment of breast cancer, prompting the investigation of novel anticancer compounds.

Purpose

In this study, we tested whether LQB-223, an 11a-N-Tosyl-5-deoxi-pterocarpan newly synthesized compound, could be effective toward breast cancer cells.

Methods

Human breast cell lines MCF-7, MDA-MB-231, HB4a and MCF-7 DoxR were used as models for this study. Cell culture, MTT and clonogenic assay, flow cytometry and Western blotting were performed.

Results

The LQB-223 decreased cell viability, inhibited colony formation and induced an expressive G2/M arrest in breast cancer cells. There was an induction in p53 and p21Cip1 protein levels following treatment of wild-type p53 MCF-7 cells, which was not observed in the mutant p53 MDA-MB-231 cell line, providing evidence that the compound might act to modulate the cell cycle regardless of p53 status. In addition, LQB-223 resulted in decreased procaspase levels and increased annexin V staining, suggesting that the apoptotic cascade is also triggered. Importantly, LQB-223 treatment was shown to be less cytotoxic to non-neoplastic breast cells than docetaxel and doxorubicin. Strikingly, exposure of doxorubicin-resistant MCF-7-DoxR cells to LQB-223 resulted in suppression of cell viability and proliferation in levels comparable to MCF-7. Of note, MCF-7-DoxR cells have an elevated expression of the P-glycoprotein efflux pump when compared to MCF-7.

Conclusion

Together, these results show that LQB-223 mediates cytotoxic effects in sensitive and resistant breast cancer cells, while presenting low toxicity to non-neoplastic cells. The new compound might represent a potential strategy to induce toxicity in breast cancer cells, especially chemoresistant cells.

Keywords

Breast cancer Drug resistance LQB-223 compound Toxicity Chemotherapeutic agents 

Notes

Acknowledgments

This work was supported by grants from Instituto Nacional de Ciência e Tecnologia (INCT), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ) and Programa de Oncobiologia. We would also like to thank Matheus Andrade Rajão for technical support.

Compliance with ethical standards

Conflict of interest

The authors confirm that this article content has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

432_2016_2212_MOESM1_ESM.doc (22 kb)
Supplementary material 1 (DOC 22 kb)
432_2016_2212_MOESM2_ESM.pdf (648 kb)
Supplementary material 2 (PDF 648 kb)
432_2016_2212_MOESM3_ESM.pdf (308 kb)
Supplementary material 3 (PDF 307 kb)
432_2016_2212_MOESM4_ESM.pdf (247 kb)
Supplementary material 4 (PDF 246 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Lauana Greicy Tonon Lemos
    • 1
    • 2
  • Gabriela Nestal de Moraes
    • 1
  • Deborah Delbue
    • 1
    • 2
  • Flavia da Cunha Vasconcelos
    • 1
  • Paula Sabbo Bernardo
    • 1
    • 2
  • Eric W–F. Lam
    • 3
  • Camilla Djenne Buarque
    • 4
  • Paulo Ribeiro Costa
    • 5
  • Raquel Ciuvalschi Maia
    • 1
    Email author
  1. 1.Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia MolecularInstituto Nacional de Câncer (INCA)Rio de JaneiroBrazil
  2. 2.Programa de Pós-Graduação Strictu Sensu em OncologiaINCARio de JaneiroBrazil
  3. 3.Department of Surgery and CancerImperial College LondonLondonUK
  4. 4.Departamento de QuímicaPontifícia Universidade Católica do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais (IPPN)Universidade Federal do Rio de JaneiroRio de JaneiroBrazil

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