22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling

Detalhes bibliográficos
Autor(a) principal: Aranha, Elenn Suzany Pereira
Data de Publicação: 2021
Outros Autores: Portilho, Adrhyann Jullyanne de Sousa, Sousa, Leilane Bentes de, Silva, Emerson Lucena da, Mesquita, Felipe Pantoja, Rocha, Waldireny C., Silva, Felipe Moura Araújo da, Lima, Emerson Silva, Alves, Ana Paula Negreiros Nunes, Koolen, Hector Henrique Ferreira, Montenegro, Raquel Carvalho, Vasconcellos, Marne Carvalho de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
dARK ID: ark:/83112/001300000sfz3
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/62927
Resumo: Ethnopharmacological relevance: 22β-hydroxytingenone (22-HTG) is a quinonemethide triterpene isolated from Salacia impressifolia (Miers) A. C. Smith (family Celastraceae), which has been used in traditional medicine to treat a variety of diseases, including dengue, renal infections, rheumatism and cancer. However, the anticancer effects of 22-HTG and the underlying molecular mechanisms in melanoma cells have not yet been elucidated. Aim of the study: The present study investigated apoptosis induction and antimetastatic potencial of 22-HTG in SK-MEL-28 human melanoma cells. Materials and methods: First, the in vitro cytotoxic activity of 22-HTG in cultured cancer cells was evaluated. Then, cell viability was determined using the trypan blue assay in melanoma cells (SK-MEL-28), which was followed by cell cycle, annexin V-FITC/propidium iodide assays (Annexin/PI), as well as assays to evaluate mitochondrial membrane potential, production of reactive oxygen species (ROS) using flow cytometry. Fluorescence microscopy using acridine orange/ethidium bromide (AO/BE) staining was also performed. RT-qPCR was carried out to evaluate the expression of BRAF, NRAS, and KRAS genes. The anti-invasiveness potential of 22-HTG was evaluated in a three-dimensional (3D) model of reconstructed human skin. Results: 22-HTG reduced viability of SK-MEL-28 cells and caused morphological changes, as cell shrinkage, chromatin condensation, and nuclear fragmentation. Furthermore, 22-HTG caused apoptosis, which was demonstrated by increased staining with AO/BE and Annexin/PI. The apoptosis may have been caused by mitochondrial instability without the involvement of ROS production. The expression of BRAF, NRAS, and KRAS, which are important biomarkers in melanoma development, was reduced by the 22-HTG treatment. In the reconstructed skin model, 22-HTG was able to decrease the invasion capacity of melanoma cells in the dermis.
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spelling 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signalingApoptoseApoptosisMelanomaMetaloproteinase 9 da MatrizMatrix Metalloproteinase 9Proteínas Quinases Ativadas por MitógenoMitogen-Activated Protein KinasesEthnopharmacological relevance: 22β-hydroxytingenone (22-HTG) is a quinonemethide triterpene isolated from Salacia impressifolia (Miers) A. C. Smith (family Celastraceae), which has been used in traditional medicine to treat a variety of diseases, including dengue, renal infections, rheumatism and cancer. However, the anticancer effects of 22-HTG and the underlying molecular mechanisms in melanoma cells have not yet been elucidated. Aim of the study: The present study investigated apoptosis induction and antimetastatic potencial of 22-HTG in SK-MEL-28 human melanoma cells. Materials and methods: First, the in vitro cytotoxic activity of 22-HTG in cultured cancer cells was evaluated. Then, cell viability was determined using the trypan blue assay in melanoma cells (SK-MEL-28), which was followed by cell cycle, annexin V-FITC/propidium iodide assays (Annexin/PI), as well as assays to evaluate mitochondrial membrane potential, production of reactive oxygen species (ROS) using flow cytometry. Fluorescence microscopy using acridine orange/ethidium bromide (AO/BE) staining was also performed. RT-qPCR was carried out to evaluate the expression of BRAF, NRAS, and KRAS genes. The anti-invasiveness potential of 22-HTG was evaluated in a three-dimensional (3D) model of reconstructed human skin. Results: 22-HTG reduced viability of SK-MEL-28 cells and caused morphological changes, as cell shrinkage, chromatin condensation, and nuclear fragmentation. Furthermore, 22-HTG caused apoptosis, which was demonstrated by increased staining with AO/BE and Annexin/PI. The apoptosis may have been caused by mitochondrial instability without the involvement of ROS production. The expression of BRAF, NRAS, and KRAS, which are important biomarkers in melanoma development, was reduced by the 22-HTG treatment. In the reconstructed skin model, 22-HTG was able to decrease the invasion capacity of melanoma cells in the dermis.Journal of Ethnopharmacology2021-12-13T12:43:56Z2021-12-13T12:43:56Z2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfARANHA, Elenn Suzany Pereira et al. 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling. Journal of Ethnopharmacology, v. 267, 113605, mar. 2021. Disponível em: http://www.repositorio.ufc.br/retrieve/144706/2021_art_eparanha.pdf. Acesso em: 13/12/2021.0378-8741http://www.repositorio.ufc.br/handle/riufc/62927ark:/83112/001300000sfz3Aranha, Elenn Suzany PereiraPortilho, Adrhyann Jullyanne de SousaSousa, Leilane Bentes deSilva, Emerson Lucena daMesquita, Felipe PantojaRocha, Waldireny C.Silva, Felipe Moura Araújo daLima, Emerson SilvaAlves, Ana Paula Negreiros NunesKoolen, Hector Henrique FerreiraMontenegro, Raquel CarvalhoVasconcellos, Marne Carvalho deengreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2021-12-13T12:43:56Zoai:repositorio.ufc.br:riufc/62927Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:17:02.379729Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
title 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
spellingShingle 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
Aranha, Elenn Suzany Pereira
Apoptose
Apoptosis
Melanoma
Metaloproteinase 9 da Matriz
Matrix Metalloproteinase 9
Proteínas Quinases Ativadas por Mitógeno
Mitogen-Activated Protein Kinases
title_short 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
title_full 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
title_fullStr 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
title_full_unstemmed 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
title_sort 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
author Aranha, Elenn Suzany Pereira
author_facet Aranha, Elenn Suzany Pereira
Portilho, Adrhyann Jullyanne de Sousa
Sousa, Leilane Bentes de
Silva, Emerson Lucena da
Mesquita, Felipe Pantoja
Rocha, Waldireny C.
Silva, Felipe Moura Araújo da
Lima, Emerson Silva
Alves, Ana Paula Negreiros Nunes
Koolen, Hector Henrique Ferreira
Montenegro, Raquel Carvalho
Vasconcellos, Marne Carvalho de
author_role author
author2 Portilho, Adrhyann Jullyanne de Sousa
Sousa, Leilane Bentes de
Silva, Emerson Lucena da
Mesquita, Felipe Pantoja
Rocha, Waldireny C.
Silva, Felipe Moura Araújo da
Lima, Emerson Silva
Alves, Ana Paula Negreiros Nunes
Koolen, Hector Henrique Ferreira
Montenegro, Raquel Carvalho
Vasconcellos, Marne Carvalho de
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Aranha, Elenn Suzany Pereira
Portilho, Adrhyann Jullyanne de Sousa
Sousa, Leilane Bentes de
Silva, Emerson Lucena da
Mesquita, Felipe Pantoja
Rocha, Waldireny C.
Silva, Felipe Moura Araújo da
Lima, Emerson Silva
Alves, Ana Paula Negreiros Nunes
Koolen, Hector Henrique Ferreira
Montenegro, Raquel Carvalho
Vasconcellos, Marne Carvalho de
dc.subject.por.fl_str_mv Apoptose
Apoptosis
Melanoma
Metaloproteinase 9 da Matriz
Matrix Metalloproteinase 9
Proteínas Quinases Ativadas por Mitógeno
Mitogen-Activated Protein Kinases
topic Apoptose
Apoptosis
Melanoma
Metaloproteinase 9 da Matriz
Matrix Metalloproteinase 9
Proteínas Quinases Ativadas por Mitógeno
Mitogen-Activated Protein Kinases
description Ethnopharmacological relevance: 22β-hydroxytingenone (22-HTG) is a quinonemethide triterpene isolated from Salacia impressifolia (Miers) A. C. Smith (family Celastraceae), which has been used in traditional medicine to treat a variety of diseases, including dengue, renal infections, rheumatism and cancer. However, the anticancer effects of 22-HTG and the underlying molecular mechanisms in melanoma cells have not yet been elucidated. Aim of the study: The present study investigated apoptosis induction and antimetastatic potencial of 22-HTG in SK-MEL-28 human melanoma cells. Materials and methods: First, the in vitro cytotoxic activity of 22-HTG in cultured cancer cells was evaluated. Then, cell viability was determined using the trypan blue assay in melanoma cells (SK-MEL-28), which was followed by cell cycle, annexin V-FITC/propidium iodide assays (Annexin/PI), as well as assays to evaluate mitochondrial membrane potential, production of reactive oxygen species (ROS) using flow cytometry. Fluorescence microscopy using acridine orange/ethidium bromide (AO/BE) staining was also performed. RT-qPCR was carried out to evaluate the expression of BRAF, NRAS, and KRAS genes. The anti-invasiveness potential of 22-HTG was evaluated in a three-dimensional (3D) model of reconstructed human skin. Results: 22-HTG reduced viability of SK-MEL-28 cells and caused morphological changes, as cell shrinkage, chromatin condensation, and nuclear fragmentation. Furthermore, 22-HTG caused apoptosis, which was demonstrated by increased staining with AO/BE and Annexin/PI. The apoptosis may have been caused by mitochondrial instability without the involvement of ROS production. The expression of BRAF, NRAS, and KRAS, which are important biomarkers in melanoma development, was reduced by the 22-HTG treatment. In the reconstructed skin model, 22-HTG was able to decrease the invasion capacity of melanoma cells in the dermis.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-13T12:43:56Z
2021-12-13T12:43:56Z
2021
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 ARANHA, Elenn Suzany Pereira et al. 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling. Journal of Ethnopharmacology, v. 267, 113605, mar. 2021. Disponível em: http://www.repositorio.ufc.br/retrieve/144706/2021_art_eparanha.pdf. Acesso em: 13/12/2021.
0378-8741
http://www.repositorio.ufc.br/handle/riufc/62927
dc.identifier.dark.fl_str_mv ark:/83112/001300000sfz3
identifier_str_mv ARANHA, Elenn Suzany Pereira et al. 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling. Journal of Ethnopharmacology, v. 267, 113605, mar. 2021. Disponível em: http://www.repositorio.ufc.br/retrieve/144706/2021_art_eparanha.pdf. Acesso em: 13/12/2021.
0378-8741
ark:/83112/001300000sfz3
url http://www.repositorio.ufc.br/handle/riufc/62927
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Journal of Ethnopharmacology
publisher.none.fl_str_mv Journal of Ethnopharmacology
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
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