Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line

Detalhes bibliográficos
Autor(a) principal: Franco, Yollanda E. M.
Data de Publicação: 2019
Outros Autores: 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.
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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spelling 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)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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