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

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Title: 11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes.
Author(s): Lemos, LG
Nestal de Moraes, G
Delbue, D
Vasconcelos, FD
Bernardo, PS
Lam, EW
Buarque, CD
Costa, PR
Maia, RC
Item Type: Journal Article
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 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.
Publication Date: 12-Aug-2016
Date of Acceptance: 26-Jul-2016
URI: http://hdl.handle.net/10044/1/43054
DOI: https://dx.doi.org/10.1007/s00432-016-2212-6
ISSN: 1432-1335
Publisher: Springer Verlag
Start Page: 2119
End Page: 2130
Journal / Book Title: Journal of Cancer Research and Clinical Oncology
Volume: 142
Issue: 10
Copyright Statement: © 2016 Springer-Verlag Berlin Heidelberg. The final publication is available at Springer via http://dx.doi.org/10.1007/s00432-016-2212-6
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: N/A
Keywords: Breast cancer
Chemotherapeutic agents
Drug resistance
LQB-223 compound
Toxicity
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Embargo Date: 2017-08-12
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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