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

  • Original Article – Cancer Research
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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.

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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.

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Authors and Affiliations

  1. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil

    Lauana Greicy Tonon Lemos, Gabriela Nestal de Moraes, Deborah Delbue, Flavia da Cunha Vasconcelos, Paula Sabbo Bernardo & Raquel Ciuvalschi Maia

  2. Programa de Pós-Graduação Strictu Sensu em Oncologia, INCA, Rio de Janeiro, Brazil

    Lauana Greicy Tonon Lemos, Deborah Delbue & Paula Sabbo Bernardo

  3. Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK

    Eric W–F. Lam

  4. Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, Brazil

    Camilla Djenne Buarque

  5. Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais (IPPN), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Paulo Ribeiro Costa

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  1. Lauana Greicy Tonon Lemos
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  2. Gabriela Nestal de Moraes
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  3. Deborah Delbue
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  4. Flavia da Cunha Vasconcelos
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  6. Eric W–F. Lam
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  8. Paulo Ribeiro Costa
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  9. Raquel Ciuvalschi Maia
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Correspondence to Raquel Ciuvalschi Maia.

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Lemos, L.G.T., Nestal de Moraes, G., Delbue, D. et al. 11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes. J Cancer Res Clin Oncol 142, 2119–2130 (2016). https://doi.org/10.1007/s00432-016-2212-6

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