A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract...

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Autores principales:	Archibald M, Pritchard T, Nehoff H, Rosengren RJ, Greish K, Taurin S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	sorafenib nilotinib castrate-resistant prostate cancer tyrosine kinase inhibitors nanomedicine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/59e61614d14143069f88a7a245383ea5
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spelling	oai:doaj.org-article:59e61614d14143069f88a7a245383ea52021-12-02T01:32:31ZA combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer1178-2013https://doaj.org/article/59e61614d14143069f88a7a245383ea52016-01-01T00:00:00Zhttps://www.dovepress.com/a-combination-of-sorafenib-and-nilotinib-reduces-the-growth-of-castrat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. Keywords: sorafenib, nilotinib, castrate-resistant prostate cancer, tyrosine kinase inhibitors, nanomedicineArchibald MPritchard TNehoff HRosengren RJGreish KTaurin SDove Medical Pressarticlesorafenibnilotinibcastrate-resistant prostate cancertyrosine kinase inhibitorsnanomedicineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 179-201 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	sorafenib nilotinib castrate-resistant prostate cancer tyrosine kinase inhibitors nanomedicine Medicine (General) R5-920
spellingShingle	sorafenib nilotinib castrate-resistant prostate cancer tyrosine kinase inhibitors nanomedicine Medicine (General) R5-920 Archibald M Pritchard T Nehoff H Rosengren RJ Greish K Taurin S A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
description	Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. Keywords: sorafenib, nilotinib, castrate-resistant prostate cancer, tyrosine kinase inhibitors, nanomedicine
format	article
author	Archibald M Pritchard T Nehoff H Rosengren RJ Greish K Taurin S
author_facet	Archibald M Pritchard T Nehoff H Rosengren RJ Greish K Taurin S
author_sort	Archibald M
title	A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
title_short	A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
title_full	A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
title_fullStr	A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
title_full_unstemmed	A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
title_sort	combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/59e61614d14143069f88a7a245383ea5
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A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

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