Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | LOCUS Repositório Institucional da UFV |
Texto Completo: | https://doi.org/10.1016/j.taap.2018.08.012 http://www.locus.ufv.br/handle/123456789/22894 |
Resumo: | The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers. |
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Moreira, Gabriela AlvesLima, Graziela Domingues de AlmeidaSiqueira, Raoni PaisBarros, Marcus Vinícius de AndradeAdjanohoun, Abraham Landry MahuviSantos, Viviane CorrêaBarbosa, Éverton de Almeida AlvesLoterio, Robson KriigerPaiva, Janine Cerqueira deGonçalves, Victor Hugo SousaViol, Lívia Cristina de SouzaMarques-da-Silva, Eduardo de AlmeidaSilva Júnior, AbelardoAlmeida, Márcia RogériaFietto, Juliana Lopes RangelMachado-Neves, MarianaFerreira, Rafaela Salgadoet al.2019-01-02T19:30:34Z2019-01-02T19:30:34Z2018-10-010041-008Xhttps://doi.org/10.1016/j.taap.2018.08.012http://www.locus.ufv.br/handle/123456789/22894The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers.engToxicology and Applied PharmacologyVolume 356, Pages 214- 223, October 20182018 Elsevier Inc. All rights reserved.info:eu-repo/semantics/openAccessSerine/Arginine-richProtein kinasesMetastasisMelanomaSRVIC compoundsAntimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdfTexto completoapplication/pdf2806116https://locus.ufv.br//bitstream/123456789/22894/1/artigo.pdfe6d6ccc68ae7a5331075eb1885e28980MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/22894/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52123456789/228942019-01-02 16:40:01.676oai:locus.ufv.br:123456789/22894Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452019-01-02T19:40:01LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false |
dc.title.en.fl_str_mv |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
title |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
spellingShingle |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma Moreira, Gabriela Alves Serine/Arginine-rich Protein kinases Metastasis Melanoma SRVIC compounds |
title_short |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
title_full |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
title_fullStr |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
title_full_unstemmed |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
title_sort |
Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
author |
Moreira, Gabriela Alves |
author_facet |
Moreira, Gabriela Alves Lima, Graziela Domingues de Almeida Siqueira, Raoni Pais Barros, Marcus Vinícius de Andrade Adjanohoun, Abraham Landry Mahuvi Santos, Viviane Corrêa Barbosa, Éverton de Almeida Alves Loterio, Robson Kriiger Paiva, Janine Cerqueira de Gonçalves, Victor Hugo Sousa Viol, Lívia Cristina de Souza Marques-da-Silva, Eduardo de Almeida Silva Júnior, Abelardo Almeida, Márcia Rogéria Fietto, Juliana Lopes Rangel Machado-Neves, Mariana Ferreira, Rafaela Salgado et al. |
author_role |
author |
author2 |
Lima, Graziela Domingues de Almeida Siqueira, Raoni Pais Barros, Marcus Vinícius de Andrade Adjanohoun, Abraham Landry Mahuvi Santos, Viviane Corrêa Barbosa, Éverton de Almeida Alves Loterio, Robson Kriiger Paiva, Janine Cerqueira de Gonçalves, Victor Hugo Sousa Viol, Lívia Cristina de Souza Marques-da-Silva, Eduardo de Almeida Silva Júnior, Abelardo Almeida, Márcia Rogéria Fietto, Juliana Lopes Rangel Machado-Neves, Mariana Ferreira, Rafaela Salgado et al. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Moreira, Gabriela Alves Lima, Graziela Domingues de Almeida Siqueira, Raoni Pais Barros, Marcus Vinícius de Andrade Adjanohoun, Abraham Landry Mahuvi Santos, Viviane Corrêa Barbosa, Éverton de Almeida Alves Loterio, Robson Kriiger Paiva, Janine Cerqueira de Gonçalves, Victor Hugo Sousa Viol, Lívia Cristina de Souza Marques-da-Silva, Eduardo de Almeida Silva Júnior, Abelardo Almeida, Márcia Rogéria Fietto, Juliana Lopes Rangel Machado-Neves, Mariana Ferreira, Rafaela Salgado et al. |
dc.subject.pt-BR.fl_str_mv |
Serine/Arginine-rich Protein kinases Metastasis Melanoma SRVIC compounds |
topic |
Serine/Arginine-rich Protein kinases Metastasis Melanoma SRVIC compounds |
description |
The Serine/arginine-rich protein kinases (SRPK) are involved in pre-mRNA splicing control through the phosphorylation of the SR protein family of splicing factors. Over the last years, several studies have shown the relevance of SRPK for human cancers and their potential as promising drug targets. In this context, we have previously selected three trifluoromethyl arylamides (named here as SRVIC24, SRVIC30 and SRVIC36) with improved in vitro antileukemia effect and ability of impairing the cellular activity of SRPK. Given the increasing amount of reports on the implication of these kinases in metastatic cancers, in this study, we have evaluated the antimetastatic effect of these compounds and the known SRPK inhibitor (SRPIN340) on a murine model of metastatic melanoma. The compounds were able to impact the melanoma cell metastatic behavior by decreasing migration, invasion, adhesion, and colony formation in in vitro assays. Also, they presented antimetastatic in vivo activity, without apparent signs of systemic toxicity after treatments, as revealed by the histology of organs and analysis of key serum biochemical markers. Moreover, the effect of the treatments on SRPK1 nuclear translocation and SR protein phosphorylation was observed. Finally, molecular docking studies were carried out to gain structural information on the SRPK-compound complexes. Together, these data suggest that SRPK pharmacological inhibition should be considered as an interesting therapeutic strategy against metastatic cancers. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-10-01 |
dc.date.accessioned.fl_str_mv |
2019-01-02T19:30:34Z |
dc.date.available.fl_str_mv |
2019-01-02T19:30:34Z |
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://doi.org/10.1016/j.taap.2018.08.012 http://www.locus.ufv.br/handle/123456789/22894 |
dc.identifier.issn.none.fl_str_mv |
0041-008X |
identifier_str_mv |
0041-008X |
url |
https://doi.org/10.1016/j.taap.2018.08.012 http://www.locus.ufv.br/handle/123456789/22894 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofseries.pt-BR.fl_str_mv |
Volume 356, Pages 214- 223, October 2018 |
dc.rights.driver.fl_str_mv |
2018 Elsevier Inc. All rights reserved. info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
2018 Elsevier Inc. All rights reserved. |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Toxicology and Applied Pharmacology |
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Toxicology and Applied Pharmacology |
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reponame:LOCUS Repositório Institucional da UFV instname:Universidade Federal de Viçosa (UFV) instacron:UFV |
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Universidade Federal de Viçosa (UFV) |
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UFV |
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UFV |
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LOCUS Repositório Institucional da UFV |
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LOCUS Repositório Institucional da UFV |
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