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

Detalhes bibliográficos
Autor(a) principal: Seba, Viviane
Data de Publicação: 2018
Outros Autores: Silva, Gabriel, Dos Santos, Mariana Bastos [UNESP], Baek, Seung Joon, França, Suzelei de Castro, Fachin, Ana Lúcia, Regasini, Luis Octavio [UNESP], Marins, Mozart
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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spelling 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
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