Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Gradua&...

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Autores principales: Yurgel VC, Oliveira CP, Begnini KR, Schultze E, Thurow HS, Leon PMM, Dellagostin OA, Campos VF, Beck RC, Guterres SS, Collares T, Pohlmann AR, Seixas FK
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:8e6ee01d18de43bda3c5c687c86fa8072021-12-02T01:19:52ZMethotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line1178-2013https://doaj.org/article/8e6ee01d18de43bda3c5c687c86fa8072014-03-01T00:00:00Zhttp://www.dovepress.com/methotrexate-diethyl-ester-loaded-lipid-core-nanocapsules-in-aqueous-s-a16249https://doaj.org/toc/1178-2013 Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Graduação em Biotecnologia (PPGB), Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil*These authors contributed equally to this workAbstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.Keywords: MTX derivative, resistance, apoptotic cell death, cell cycle arrest, nanocarriers, drug delivery, drug targetingYurgel VCOliveira CPBegnini KRSchultze EThurow HSLeon PMMDellagostin OACampos VFBeck RCGuterres SSCollares TPohlmann ARSeixas FKDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1583-1591 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Yurgel VC
Oliveira CP
Begnini KR
Schultze E
Thurow HS
Leon PMM
Dellagostin OA
Campos VF
Beck RC
Guterres SS
Collares T
Pohlmann AR
Seixas FK
Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
description Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas11Programa de Pós-Graduação em Biotecnologia (PPGB), Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil*These authors contributed equally to this workAbstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.Keywords: MTX derivative, resistance, apoptotic cell death, cell cycle arrest, nanocarriers, drug delivery, drug targeting
format article
author Yurgel VC
Oliveira CP
Begnini KR
Schultze E
Thurow HS
Leon PMM
Dellagostin OA
Campos VF
Beck RC
Guterres SS
Collares T
Pohlmann AR
Seixas FK
author_facet Yurgel VC
Oliveira CP
Begnini KR
Schultze E
Thurow HS
Leon PMM
Dellagostin OA
Campos VF
Beck RC
Guterres SS
Collares T
Pohlmann AR
Seixas FK
author_sort Yurgel VC
title Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
title_short Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
title_full Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
title_fullStr Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
title_full_unstemmed Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
title_sort methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/8e6ee01d18de43bda3c5c687c86fa807
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