Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3390/ijms19102846 http://hdl.handle.net/1843/56293 https://orcid.org/0000-0002-7070-4412 https://orcid.org/0000-0002-4370-0803 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9980-3169 |
Resumo: | Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma, increased in vitro DNA fragmentation and decreased cell adhesion. Here, we present some molecular and cellular events related to the antimetastatic effect induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10 and melanocyte Melan-a. Using difference gel electrophoresis and mass spectrometry, we identified four proteins overexpressed in tumor cells, all of them related to proliferation, survival, migration and cell invasion, that had their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat shock protein 65, calcyclin binding protein and eukaryotic translation initiation factor 4H. In addition, some antioxidant and glycolytic enzymes show increased expression after exposure to CMS-2, along with an induction of melanogenesis (differentiation marker). The down regulation of cofilin 1, a protein involved in cell motility, may explain the inhibition of cell migration and dendritic-like outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together, it is argued that CMS-2 modulates the expression of proteins related to metastatic development, driving the cell to a more differentiated-like state. These effects support the CMS-2 antimetastatic activity and place this fraction in the category of anticancer agent. |
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2023-07-14T20:29:49Z2023-07-14T20:29:49Z2018-09-201910https://doi.org/10.3390/ijms191028461422-0067http://hdl.handle.net/1843/56293https://orcid.org/0000-0002-7070-4412https://orcid.org/0000-0002-4370-0803https://orcid.org/0000-0003-2823-4530https://orcid.org/0000-0001-9980-3169Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma, increased in vitro DNA fragmentation and decreased cell adhesion. Here, we present some molecular and cellular events related to the antimetastatic effect induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10 and melanocyte Melan-a. Using difference gel electrophoresis and mass spectrometry, we identified four proteins overexpressed in tumor cells, all of them related to proliferation, survival, migration and cell invasion, that had their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat shock protein 65, calcyclin binding protein and eukaryotic translation initiation factor 4H. In addition, some antioxidant and glycolytic enzymes show increased expression after exposure to CMS-2, along with an induction of melanogenesis (differentiation marker). The down regulation of cofilin 1, a protein involved in cell motility, may explain the inhibition of cell migration and dendritic-like outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together, it is argued that CMS-2 modulates the expression of proteins related to metastatic development, driving the cell to a more differentiated-like state. These effects support the CMS-2 antimetastatic activity and place this fraction in the category of anticancer agent.Estudos anteriores mostraram que P1G10, uma fração proteolítica do látex de Vasconcellea cundinamarcensis, reduziu a massa tumoral em animais portadores de melanoma, aumentou a fragmentação do DNA in vitro e diminuiu a adesão celular. Aqui, apresentamos alguns eventos moleculares e celulares relacionados ao efeito antimetastático induzido pela fração CMS-2 derivada de P1G10 em melanoma metastático B16-F10 e melanócito Melan-a. Utilizando eletroforese em gel de diferença e espectrometria de massas, identificamos quatro proteínas superexpressas em células tumorais, todas relacionadas à proliferação, sobrevivência, migração e invasão celular, que tiveram sua expressão normalizada após o tratamento com CMS-2: nucleofosmina 1, proteína de choque térmico 65 , proteína de ligação à calciclina e fator de iniciação da tradução eucariótica 4H. Além disso, algumas enzimas antioxidantes e glicolíticas apresentam expressão aumentada após a exposição ao CMS-2, juntamente com a indução da melanogênese (marcador de diferenciação). A regulação negativa da cofilina 1, uma proteína envolvida na motilidade celular, pode explicar a inibição da migração celular e o crescimento dendrítico em B16-F10 e Melan-a, observados após o tratamento com CMS-2. Em conjunto, argumenta-se que o CMS-2 modula a expressão de proteínas relacionadas ao desenvolvimento metastático, conduzindo a célula a um estado semelhante mais diferenciado. Esses efeitos suportam a atividade antimetastática do CMS-2 e colocam essa fração na categoria de agente anticancerígeno.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE FARMACOLOGIAICB - DEPARTAMENTO DE PARASITOLOGIAInternational Journal of Molecular SciencesCisteína proteasesMelanomaMovimento celularDiferenciação celularCysteine proteasesAntimetastaticMelanomaCell migrationMelanogenesisCell differentiationCysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiationCisteína proteases de V. cundinamarcensis (C. candamarcensis) inibem a metástase do melanoma e modulam a expressão de proteínas relacionadas à proliferação, migração e diferenciaçãoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.mdpi.com/1422-0067/19/10/2846Fernanda de Oliveira LemosDalton Dittz JúniorVerlane Gonçalves SantosSimone da Fonseca PiresHélida Monteiro de AndradeCarlos Edmundo Salas BravoMiriam Teresa Paz Lopesapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56293/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALCysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation.pdfCysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation.pdfapplication/pdf49423075https://repositorio.ufmg.br/bitstream/1843/56293/2/Cysteine%20proteases%20from%20V.%20cundinamarcensis%20%28C.%20candamarcensis%29%20inhibit%20melanoma%20metastasis%20and%20modulate%20expression%20of%20proteins%20related%20to%20proliferation%2c%20migration%20and%20differentiation.pdfbad8a912823cb05f8b4e3ff1dff0f769MD521843/562932023-07-14 17:29:49.572oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-14T20:29:49Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
dc.title.alternative.pt_BR.fl_str_mv |
Cisteína proteases de V. cundinamarcensis (C. candamarcensis) inibem a metástase do melanoma e modulam a expressão de proteínas relacionadas à proliferação, migração e diferenciação |
title |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
spellingShingle |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation Fernanda de Oliveira Lemos Cysteine proteases Antimetastatic Melanoma Cell migration Melanogenesis Cell differentiation Cisteína proteases Melanoma Movimento celular Diferenciação celular |
title_short |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
title_full |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
title_fullStr |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
title_full_unstemmed |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
title_sort |
Cysteine proteases from V. cundinamarcensis (C. candamarcensis) inhibit melanoma metastasis and modulate expression of proteins related to proliferation, migration and differentiation |
author |
Fernanda de Oliveira Lemos |
author_facet |
Fernanda de Oliveira Lemos Dalton Dittz Júnior Verlane Gonçalves Santos Simone da Fonseca Pires Hélida Monteiro de Andrade Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes |
author_role |
author |
author2 |
Dalton Dittz Júnior Verlane Gonçalves Santos Simone da Fonseca Pires Hélida Monteiro de Andrade Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Fernanda de Oliveira Lemos Dalton Dittz Júnior Verlane Gonçalves Santos Simone da Fonseca Pires Hélida Monteiro de Andrade Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes |
dc.subject.por.fl_str_mv |
Cysteine proteases Antimetastatic Melanoma Cell migration Melanogenesis Cell differentiation |
topic |
Cysteine proteases Antimetastatic Melanoma Cell migration Melanogenesis Cell differentiation Cisteína proteases Melanoma Movimento celular Diferenciação celular |
dc.subject.other.pt_BR.fl_str_mv |
Cisteína proteases Melanoma Movimento celular Diferenciação celular |
description |
Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma, increased in vitro DNA fragmentation and decreased cell adhesion. Here, we present some molecular and cellular events related to the antimetastatic effect induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10 and melanocyte Melan-a. Using difference gel electrophoresis and mass spectrometry, we identified four proteins overexpressed in tumor cells, all of them related to proliferation, survival, migration and cell invasion, that had their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat shock protein 65, calcyclin binding protein and eukaryotic translation initiation factor 4H. In addition, some antioxidant and glycolytic enzymes show increased expression after exposure to CMS-2, along with an induction of melanogenesis (differentiation marker). The down regulation of cofilin 1, a protein involved in cell motility, may explain the inhibition of cell migration and dendritic-like outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together, it is argued that CMS-2 modulates the expression of proteins related to metastatic development, driving the cell to a more differentiated-like state. These effects support the CMS-2 antimetastatic activity and place this fraction in the category of anticancer agent. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-09-20 |
dc.date.accessioned.fl_str_mv |
2023-07-14T20:29:49Z |
dc.date.available.fl_str_mv |
2023-07-14T20:29:49Z |
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 |
http://hdl.handle.net/1843/56293 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3390/ijms19102846 |
dc.identifier.issn.pt_BR.fl_str_mv |
1422-0067 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-7070-4412 https://orcid.org/0000-0002-4370-0803 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9980-3169 |
url |
https://doi.org/10.3390/ijms19102846 http://hdl.handle.net/1843/56293 https://orcid.org/0000-0002-7070-4412 https://orcid.org/0000-0002-4370-0803 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9980-3169 |
identifier_str_mv |
1422-0067 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
International Journal of Molecular Sciences |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE FARMACOLOGIA ICB - DEPARTAMENTO DE PARASITOLOGIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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