title: 11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes.
abstract: Multidrug resistance is the major obstacle for successful treatment of breast cancer, prompting the investigation of novel anticancer compounds.
  
  
  OBJECTIVE
  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 Dox(R) 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 p21(Cip1) 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-Dox(R) cells to LQB-223 resulted in suppression of cell viability and proliferation in levels comparable to MCF-7. Of note, MCF-7-Dox(R) cells have an elevated expression of the P-glycoprotein efflux pump when compared to MCF-7.
  
  
  CONCLUSIONS
  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.
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.|Programa de Pós-Graduação Strictu Sensu em Oncologia, INCA, Rio de Janeiro, Brazil.
authors: Lauana Greicy Tonon
authors: LG
authors: Lemos
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
authors: Gabriela
authors: G
authors: Nestal de Moraes
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.|Programa de Pós-Graduação Strictu Sensu em Oncologia, INCA, Rio de Janeiro, Brazil.
authors: Deborah
authors: D
authors: Delbue
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
authors: Flavia da Cunha
authors: Fda C
authors: Vasconcelos
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.|Programa de Pós-Graduação Strictu Sensu em Oncologia, INCA, Rio de Janeiro, Brazil.
authors: Paula Sabbo
authors: PS
authors: Bernardo
authors: Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors: Eric W-F
authors: EW
authors: Lam
authors: Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Camilla Djenne
authors: CD
authors: Buarque
authors: Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais (IPPN), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Paulo Ribeiro
authors: PR
authors: Costa
authors: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil. rcmaia@inca.gov.br.
authors: Raquel Ciuvalschi
authors: RC
authors: Maia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D010641:Phenotype; D036343:Pterocarpans / Q000009:adverse effects / Q000494:pharmacology*; D043823:Taxoids / Q000009:adverse effects / Q000494:pharmacology
chemical_list: C000593733:11a-N-tosyl-5-deoxi-pterocarpan; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D036343:Pterocarpans; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin
keywords: Breast cancer; Chemotherapeutic agents; Drug resistance; LQB-223 compound; Toxicity