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The LQB-223 Compound Modulates Antiapoptotic Proteins and Impairs Breast Cancer Cell Growth and Migration

1
Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional do Câncer (INCA). Praça da Cruz Vermelha, 23, 6 andar, Rio de Janeiro (RJ) 20230 130, Brazil
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Programa de Pós-Graduação Strictu Sensu em Oncologia, INCA. Rua André Cavalcanti, 37, 2° andar, Centro, RJ 20 231-050, Brazil
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Programa de Oncobiologia Celular e Molecular, INCA. Praça da Cruz Vermelha, 23, 6 andar, Centro, RJ 20 231-050, Brazil
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Departamento de Ciências da Natureza, Instituto de Humanidades e Saúde, Universidade Federal Fluminense (UFF), Rua Recife 1-7, Bela Vista, Rio das Ostras, RJ 28880-000, Brazil
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Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais (IPPN), Universidade Federal do Rio de Janeiro, CCS, Bloco H - Ilha do Fundão, RJ 21941-902, Brazil
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Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rua Marquês de São Vicente 225, Gávea, RJ 22435-900, Brazil
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5063; https://doi.org/10.3390/ijms20205063
Received: 28 August 2019 / Revised: 7 October 2019 / Accepted: 9 October 2019 / Published: 12 October 2019
(This article belongs to the Section Molecular Oncology)
Drug resistance represents a major issue in treating breast cancer, despite the identification of novel therapeutic strategies, biomarkers, and subgroups. We have previously identified the LQB-223, 11a-N-Tosyl-5-deoxi-pterocarpan, as a promising compound in sensitizing doxorubicin-resistant breast cancer cells, with little toxicity to non-neoplastic cells. Here, we investigated the mechanisms underlying LQB-223 antitumor effects in 2D and 3D models of breast cancer. MCF-7 and MDA-MB-231 cells had migration and motility profile assessed by wound-healing and phagokinetic track motility assays, respectively. Cytotoxicity in 3D conformation was evaluated by measuring spheroid size and performing acid phosphatase and gelatin migration assays. Protein expression was analyzed by immunoblotting. Our results show that LQB-223, but not doxorubicin treatment, suppressed the migratory and motility capacity of breast cancer cells. In 3D conformation, LQB-223 remarkably decreased cell viability, as well as reduced 3D culture size and migration. Mechanistically, LQB-223-mediated anticancer effects involved decreased proteins levels of XIAP, c-IAP1, and Mcl-1 chemoresistance-related proteins, but not survivin. Survivin knockdown partially potentiated LQB-223-induced cytotoxicity. Additionally, cell treatment with LQB-223 resulted in changes in the mRNA levels of epithelial-mesenchymal transition markers, suggesting that it might modulate cell plasticity. Our data demonstrate that LQB-223 impairs 3D culture growth and migration in 2D and 3D models of breast cancer exhibiting different phenotypes. View Full-Text
Keywords: breast cancer; drug resistance; LQB-223 compound breast cancer; drug resistance; LQB-223 compound
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Lemos, L.G.T.; Longo, G.M.C.; Mendonça, B.S.; Robaina, M.C.; Brum, M.C.M.; Cirilo, C.A.; Gimba, E.R.P.; Costa, P.R.R.; Buarque, C.D.; Nestal de Moraes, G.; Maia, R.C. The LQB-223 Compound Modulates Antiapoptotic Proteins and Impairs Breast Cancer Cell Growth and Migration. Int. J. Mol. Sci. 2019, 20, 5063.

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