Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes
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 UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms19092838 http://hdl.handle.net/11449/186885 |
Resumo: | Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings. These compounds exhibit anticancer activity against a variety of tumor cell lines through multiple mechanisms, including the regulation of the tumor-suppressor protein p53 and its target genes. An important process regulated by p53 is epithelial-mesenchymal transition (EMT), which facilitates tumor metastasis by conferring migratory and invasive properties to cancer cells. The activation of p53 can revert EMT and reduce migration and invasion. This study aimed to examine the inhibitory effects of two 4′-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53−/−) OS cell lines as well as the underlying molecular mechanisms. Cell viability was examined by MTT assay. Transwell assays were used to evaluate the migratory and invasive ability of the cells. The two 4′-aminochalcones showed low capacity to inhibit the viability of OS cells independent of p53 status, but preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line expressing p53. Invasion was strongly inhibited by both chalcones independent of p53 status. RT-PCR, zymography, and Western blot were used to study the expression of matrix metalloproteinases and EMT markers after treatment with the chalcones. The results indicated that the 4′-aminochalcone-induced antimigratory and anti-invasive effects are potentially associated with the inhibition of extracellular matrix (ECM) enzymatic degradation in OS cells and with the modulation of EMT genes. These effects probably result from the induced increase of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and D15 have potential anti-metastatic activity mediated by p53 that can be exploited for OS treatment. |
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Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genesChalconesEpithelial-mesenchymal transitionInvasionMigrationOsteosarcomaP53Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings. These compounds exhibit anticancer activity against a variety of tumor cell lines through multiple mechanisms, including the regulation of the tumor-suppressor protein p53 and its target genes. An important process regulated by p53 is epithelial-mesenchymal transition (EMT), which facilitates tumor metastasis by conferring migratory and invasive properties to cancer cells. The activation of p53 can revert EMT and reduce migration and invasion. This study aimed to examine the inhibitory effects of two 4′-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53−/−) OS cell lines as well as the underlying molecular mechanisms. Cell viability was examined by MTT assay. Transwell assays were used to evaluate the migratory and invasive ability of the cells. The two 4′-aminochalcones showed low capacity to inhibit the viability of OS cells independent of p53 status, but preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line expressing p53. Invasion was strongly inhibited by both chalcones independent of p53 status. RT-PCR, zymography, and Western blot were used to study the expression of matrix metalloproteinases and EMT markers after treatment with the chalcones. The results indicated that the 4′-aminochalcone-induced antimigratory and anti-invasive effects are potentially associated with the inhibition of extracellular matrix (ECM) enzymatic degradation in OS cells and with the modulation of EMT genes. These effects probably result from the induced increase of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and D15 have potential anti-metastatic activity mediated by p53 that can be exploited for OS treatment.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Biotechnology Unit University of Ribeirão PretoLaboratory of Green and Medicinal Chemistry Department of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)Laboratory of Signal Transduction College of Veterinary Medicine and Research Institute for Veterinary Science Seoul National UniversityMedicine School University of Ribeirão PretoLaboratory of Green and Medicinal Chemistry Department of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)FAPESP: 2014/15307-7;2017/03237-2University of Ribeirão PretoUniversidade Estadual Paulista (Unesp)Seoul National UniversitySeba, VivianeSilva, GabrielDos Santos, Mariana Bastos [UNESP]Baek, Seung JoonFrança, Suzelei de CastroFachin, Ana LúciaRegasini, Luis Octavio [UNESP]Marins, Mozart2019-10-06T15:18:42Z2019-10-06T15:18:42Z2018-09-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms19092838International Journal of Molecular Sciences, v. 19, n. 9, 2018.1422-00671661-6596http://hdl.handle.net/11449/18688510.3390/ijms190928382-s2.0-85053726112Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Sciencesinfo:eu-repo/semantics/openAccess2021-10-23T20:19:26Zoai:repositorio.unesp.br:11449/186885Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:41:28.761239Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
title |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
spellingShingle |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes Seba, Viviane Chalcones Epithelial-mesenchymal transition Invasion Migration Osteosarcoma P53 |
title_short |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
title_full |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
title_fullStr |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
title_full_unstemmed |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
title_sort |
Chalcone derivatives 4′-amino-1-naphthyl-chalcone (D14) and 4′-amino-4-methyl-1-naphthyl-chalcone (D15) suppress migration and invasion of osteosarcoma cells mediated by p53 regulating emt-related genes |
author |
Seba, Viviane |
author_facet |
Seba, Viviane Silva, Gabriel Dos Santos, Mariana Bastos [UNESP] Baek, Seung Joon França, Suzelei de Castro Fachin, Ana Lúcia Regasini, Luis Octavio [UNESP] Marins, Mozart |
author_role |
author |
author2 |
Silva, Gabriel Dos Santos, Mariana Bastos [UNESP] Baek, Seung Joon França, Suzelei de Castro Fachin, Ana Lúcia Regasini, Luis Octavio [UNESP] Marins, Mozart |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
University of Ribeirão Preto Universidade Estadual Paulista (Unesp) Seoul National University |
dc.contributor.author.fl_str_mv |
Seba, Viviane Silva, Gabriel Dos Santos, Mariana Bastos [UNESP] Baek, Seung Joon França, Suzelei de Castro Fachin, Ana Lúcia Regasini, Luis Octavio [UNESP] Marins, Mozart |
dc.subject.por.fl_str_mv |
Chalcones Epithelial-mesenchymal transition Invasion Migration Osteosarcoma P53 |
topic |
Chalcones Epithelial-mesenchymal transition Invasion Migration Osteosarcoma P53 |
description |
Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings. These compounds exhibit anticancer activity against a variety of tumor cell lines through multiple mechanisms, including the regulation of the tumor-suppressor protein p53 and its target genes. An important process regulated by p53 is epithelial-mesenchymal transition (EMT), which facilitates tumor metastasis by conferring migratory and invasive properties to cancer cells. The activation of p53 can revert EMT and reduce migration and invasion. This study aimed to examine the inhibitory effects of two 4′-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53−/−) OS cell lines as well as the underlying molecular mechanisms. Cell viability was examined by MTT assay. Transwell assays were used to evaluate the migratory and invasive ability of the cells. The two 4′-aminochalcones showed low capacity to inhibit the viability of OS cells independent of p53 status, but preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line expressing p53. Invasion was strongly inhibited by both chalcones independent of p53 status. RT-PCR, zymography, and Western blot were used to study the expression of matrix metalloproteinases and EMT markers after treatment with the chalcones. The results indicated that the 4′-aminochalcone-induced antimigratory and anti-invasive effects are potentially associated with the inhibition of extracellular matrix (ECM) enzymatic degradation in OS cells and with the modulation of EMT genes. These effects probably result from the induced increase of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and D15 have potential anti-metastatic activity mediated by p53 that can be exploited for OS treatment. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-09-19 2019-10-06T15:18:42Z 2019-10-06T15:18:42Z |
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://dx.doi.org/10.3390/ijms19092838 International Journal of Molecular Sciences, v. 19, n. 9, 2018. 1422-0067 1661-6596 http://hdl.handle.net/11449/186885 10.3390/ijms19092838 2-s2.0-85053726112 |
url |
http://dx.doi.org/10.3390/ijms19092838 http://hdl.handle.net/11449/186885 |
identifier_str_mv |
International Journal of Molecular Sciences, v. 19, n. 9, 2018. 1422-0067 1661-6596 10.3390/ijms19092838 2-s2.0-85053726112 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129347057352704 |