22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
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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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 |
_version_ |
1818373830788251648 |