Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/63223 |
Resumo: | Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of <i>Hedychium coronarium</i>, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer. |
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Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell linecoronarin Dglioblastomaapoptosiscell cycle arrestnatural productsScience & TechnologyGlioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of <i>Hedychium coronarium</i>, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.This research was funded by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/06636–7 and 2016/06137–6), financiadora de Estudos e Projetos FINEP (MCTI/FINEP/MS/SCTIE/DECIT–01/2013–FPXII–BIOPLAT).Multidisciplinary Digital Publishing InstituteUniversidade do MinhoFranco, Yollanda E. M.Okubo, Marcia Y.Torre, Adriana D.Paiva, Paula P.Rosa, Marcela N.Silva, Viviane A. O.Reis, R. M.Ruiz, Ana L. T. G.Imamura, Paulo M.Carvalho, João E. deLongato, Giovanna B.20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/63223engM. Franco, Y.E.; Y. Okubo, M.; D. Torre, A.; P. Paiva, P.; N. Rosa, M.; O. Silva, V.A.; M. Reis, R.; T. G. Ruiz, A.L.; M. Imamura, P.; de Carvalho, J.E.; B. Longato, G. Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line. Molecules 2019, 24, 4498.1420-304910.3390/molecules2424449831818017https://www.mdpi.com/1420-3049/24/24/4498info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T11:56:08Zoai:repositorium.sdum.uminho.pt:1822/63223Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:45:44.493063Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
title |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
spellingShingle |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line Franco, Yollanda E. M. coronarin D glioblastoma apoptosis cell cycle arrest natural products Science & Technology |
title_short |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
title_full |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
title_fullStr |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
title_full_unstemmed |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
title_sort |
Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line |
author |
Franco, Yollanda E. M. |
author_facet |
Franco, Yollanda E. M. Okubo, Marcia Y. Torre, Adriana D. Paiva, Paula P. Rosa, Marcela N. Silva, Viviane A. O. Reis, R. M. Ruiz, Ana L. T. G. Imamura, Paulo M. Carvalho, João E. de Longato, Giovanna B. |
author_role |
author |
author2 |
Okubo, Marcia Y. Torre, Adriana D. Paiva, Paula P. Rosa, Marcela N. Silva, Viviane A. O. Reis, R. M. Ruiz, Ana L. T. G. Imamura, Paulo M. Carvalho, João E. de Longato, Giovanna B. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Franco, Yollanda E. M. Okubo, Marcia Y. Torre, Adriana D. Paiva, Paula P. Rosa, Marcela N. Silva, Viviane A. O. Reis, R. M. Ruiz, Ana L. T. G. Imamura, Paulo M. Carvalho, João E. de Longato, Giovanna B. |
dc.subject.por.fl_str_mv |
coronarin D glioblastoma apoptosis cell cycle arrest natural products Science & Technology |
topic |
coronarin D glioblastoma apoptosis cell cycle arrest natural products Science & Technology |
description |
Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of <i>Hedychium coronarium</i>, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z |
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/1822/63223 |
url |
http://hdl.handle.net/1822/63223 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
M. Franco, Y.E.; Y. Okubo, M.; D. Torre, A.; P. Paiva, P.; N. Rosa, M.; O. Silva, V.A.; M. Reis, R.; T. G. Ruiz, A.L.; M. Imamura, P.; de Carvalho, J.E.; B. Longato, G. Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line. Molecules 2019, 24, 4498. 1420-3049 10.3390/molecules24244498 31818017 https://www.mdpi.com/1420-3049/24/24/4498 |
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 |
Multidisciplinary Digital Publishing Institute |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132210723291136 |