Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold

Detalhes bibliográficos
Autor(a) principal: Duarte, Diana
Data de Publicação: 2019
Outros Autores: Fraga, Alexandra Gabriel, Pedrosa, Jorge, Martel, Fátima, Vale, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/62298
Resumo: Cancer treatment is one of the major fields of interest for the scientific community. Investment in cancer research is costly but essential to provide patients with more effective and safe treatments. In this project, we describe the synthesis and characterization of new thiazole derivatives coupled to CPP2, a cell-penetrating peptide (CPP) reported for colon cancer cells. Using a human adenocarcinoma-derived cell line (Caco-2), these new CPPs were evaluated for antiproliferative (3H-thymidine incorporation) and cytotoxic effect (extracellular lactate dehydrogenase activity). One of these derivatives, the BTZCA thiazole compound and its peptide-conjugated (BTZCA-CPP2) also showed the ability to decrease tumour cell viability and proliferation, with potential cytotoxic effect against human breast cancer MCF-7 cells. Then, cytotoxicity studies were developed against J774, L929 and THP1 cell lines and this new family showed no significant cytotoxicity, when compared to their counterparts alone (BTZCA and CPP2). The use of smaller CPP conjugated with this family of derivatives can be also considered in future for the development of new drugs to cancer therapy.
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spelling Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffoldCell-penetrating peptideCPP2ThiazoleMCF-7Caco-2Cell-penetrating peptidesScience & TechnologyCancer treatment is one of the major fields of interest for the scientific community. Investment in cancer research is costly but essential to provide patients with more effective and safe treatments. In this project, we describe the synthesis and characterization of new thiazole derivatives coupled to CPP2, a cell-penetrating peptide (CPP) reported for colon cancer cells. Using a human adenocarcinoma-derived cell line (Caco-2), these new CPPs were evaluated for antiproliferative (3H-thymidine incorporation) and cytotoxic effect (extracellular lactate dehydrogenase activity). One of these derivatives, the BTZCA thiazole compound and its peptide-conjugated (BTZCA-CPP2) also showed the ability to decrease tumour cell viability and proliferation, with potential cytotoxic effect against human breast cancer MCF-7 cells. Then, cytotoxicity studies were developed against J774, L929 and THP1 cell lines and this new family showed no significant cytotoxicity, when compared to their counterparts alone (BTZCA and CPP2). The use of smaller CPP conjugated with this family of derivatives can be also considered in future for the development of new drugs to cancer therapy.This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia, in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01- 0145-FEDER-007274)." This work was also financed by FCT and FEDER (European Union), through project IF/00092/2014/CP1255/CT0004. NV thanks FCT by IF position, DQB-Faculty of Sciences from University of Porto, for support in peptide synthesis, and Fundação Manuel António da Mota by support Nuno Vale Lab. DD thanks FCT for PhD grant with ref. SFRH/BD/140734/2018. AGF and JP were involved in the cytotoxicity assays, which were developed within the scope of the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement through FEDER. This work was also financed through the Competitiveness Factors Operational Programme (COMPETE) and by national funds, through FCT, under the scope of the project POCI-01- 0145-FEDER-007038. AGF would also like to acknowledge FCT for the post-doc fellow SFRH/BPD/112903/2015. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT or FMAM.ElsevierUniversidade do MinhoDuarte, DianaFraga, Alexandra GabrielPedrosa, JorgeMartel, FátimaVale, Nuno2019-10-052019-10-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/62298eng0014-29991879-071210.1016/j.ejphar.2019.17255431326378info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:32:43Zoai:repositorium.sdum.uminho.pt:1822/62298Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:28:06.316679Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
title Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
spellingShingle Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
Duarte, Diana
Cell-penetrating peptide
CPP2
Thiazole
MCF-7
Caco-2
Cell-penetrating peptides
Science & Technology
title_short Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
title_full Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
title_fullStr Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
title_full_unstemmed Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
title_sort Increasing the potential of cell-penetrating peptides for cancer therapy using a new pentagonal scaffold
author Duarte, Diana
author_facet Duarte, Diana
Fraga, Alexandra Gabriel
Pedrosa, Jorge
Martel, Fátima
Vale, Nuno
author_role author
author2 Fraga, Alexandra Gabriel
Pedrosa, Jorge
Martel, Fátima
Vale, Nuno
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Duarte, Diana
Fraga, Alexandra Gabriel
Pedrosa, Jorge
Martel, Fátima
Vale, Nuno
dc.subject.por.fl_str_mv Cell-penetrating peptide
CPP2
Thiazole
MCF-7
Caco-2
Cell-penetrating peptides
Science & Technology
topic Cell-penetrating peptide
CPP2
Thiazole
MCF-7
Caco-2
Cell-penetrating peptides
Science & Technology
description Cancer treatment is one of the major fields of interest for the scientific community. Investment in cancer research is costly but essential to provide patients with more effective and safe treatments. In this project, we describe the synthesis and characterization of new thiazole derivatives coupled to CPP2, a cell-penetrating peptide (CPP) reported for colon cancer cells. Using a human adenocarcinoma-derived cell line (Caco-2), these new CPPs were evaluated for antiproliferative (3H-thymidine incorporation) and cytotoxic effect (extracellular lactate dehydrogenase activity). One of these derivatives, the BTZCA thiazole compound and its peptide-conjugated (BTZCA-CPP2) also showed the ability to decrease tumour cell viability and proliferation, with potential cytotoxic effect against human breast cancer MCF-7 cells. Then, cytotoxicity studies were developed against J774, L929 and THP1 cell lines and this new family showed no significant cytotoxicity, when compared to their counterparts alone (BTZCA and CPP2). The use of smaller CPP conjugated with this family of derivatives can be also considered in future for the development of new drugs to cancer therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-05
2019-10-05T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/1822/62298
url https://hdl.handle.net/1822/62298
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0014-2999
1879-0712
10.1016/j.ejphar.2019.172554
31326378
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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