Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of cancer research and clinical oncology, 2016-10, Vol.142 (10), p.2119-2130

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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. 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.