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https://locus.ufv.br//handle/123456789/22894
Tipo: | Artigo |
Título: | Antimetastatic effect of the pharmacological inhibition of serine/arginine-rich protein kinases (SRPK) in murine melanoma |
Autor(es): | 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. |
Abstract: | 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. |
Palavras-chave: | Serine/Arginine-rich Protein kinases Metastasis Melanoma SRVIC compounds |
Editor: | Toxicology and Applied Pharmacology |
Tipo de Acesso: | 2018 Elsevier Inc. All rights reserved. |
URI: | https://doi.org/10.1016/j.taap.2018.08.012 http://www.locus.ufv.br/handle/123456789/22894 |
Data do documento: | 1-Out-2018 |
Aparece nas coleções: | Artigos |
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Arquivo | Descrição | Tamanho | Formato | |
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artigo.pdf Until 2100-12-31 | Texto completo | 2,74 MB | Adobe PDF | Visualizar/Abrir ACESSO RESTRITO |
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