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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.
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ELauana APIIPaper LQB-223Paper Lau_FinalManuscript[1] EWL.doc | Accepted version | 167 kB | Microsoft Word | View/Open |
Title: | 11a-N-Tosyl-5-deoxi-pterocarpan, LQB-223, a novel compound with potent antineoplastic activity toward breast cancer cells with different phenotypes. |
Authors: | 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. |
Issue 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 |
Appears in Collections: | Department of Surgery and Cancer |