Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells

Detalhes bibliográficos
Autor(a) principal: Calcada, C.
Data de Publicação: 2014
Outros Autores: Pereira, J., Domingues, R. M. A., Silvestre, A. J. D., Duarte, F., Pereira-Wilson, C., Lima, C. F.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/20659
Resumo: Eucalyptus nitens crops are used in Portugal mainly by the pulp and paper industries, producing substantial bark residues with no added value use [1]. They can, however, be an interesting source of bioactive triterpenic compounds. Here, a lipophilic crude extract (CE) from bark of E. nitens prepared with dichloromethane [1] with about 70% (w/w) of triterpenoids, and a fraction of this (F2) more enriched in triterpenoids (93% w/w), as well as their main compounds betulinic acid (BiA) and betulonic acid (BoA), were used to determine their potential cytotoxicity against the colorectal HCT116 cancer cells. After 48h of incubation, the extracts/compounds inhibited significantly cell growth in a concentration-dependent manner (assessed by the MTT assay), with a GI50 s of 1.3 µg/mL and 2.2 µg/mL for F2 and CE extracts, respectively, and of 0.8µM and 3.9µM for BoA and BiA, respectively. The inhibition of cell growth was shown to be dependent on both the arrest of cell cycle at the G2/M phase, and the induction of cell death (assessed by PI staining). At the higher concentrations tested (up to 25µM), apoptosis was the major contributor to the observed cell death, and that was associated with JNK activation. Using the JNK inhibitor SP600125 and the pan-caspase inhibitor z-VAD, apoptosis induced by the extracts/compounds was shown to be dependent on JNK and caspases activation. At intermediate concentrations of extracts/compounds, a delayed and non-apoptotic type of cell death was present, which was associated with a significant activation of AMPK and a decrease of p53 levels. Altogether, these results demonstrate that the wasted bark of E. nitens can be used as a potential source of interesting cytotoxic natural triterpenoids against cancer cells.
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spelling Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cellsEucalyptus nitensbark extractstriterpenoidsHCT116 cancer cellscytotoxicityapoptosiscell cycle arrestEucalyptus nitens crops are used in Portugal mainly by the pulp and paper industries, producing substantial bark residues with no added value use [1]. They can, however, be an interesting source of bioactive triterpenic compounds. Here, a lipophilic crude extract (CE) from bark of E. nitens prepared with dichloromethane [1] with about 70% (w/w) of triterpenoids, and a fraction of this (F2) more enriched in triterpenoids (93% w/w), as well as their main compounds betulinic acid (BiA) and betulonic acid (BoA), were used to determine their potential cytotoxicity against the colorectal HCT116 cancer cells. After 48h of incubation, the extracts/compounds inhibited significantly cell growth in a concentration-dependent manner (assessed by the MTT assay), with a GI50 s of 1.3 µg/mL and 2.2 µg/mL for F2 and CE extracts, respectively, and of 0.8µM and 3.9µM for BoA and BiA, respectively. The inhibition of cell growth was shown to be dependent on both the arrest of cell cycle at the G2/M phase, and the induction of cell death (assessed by PI staining). At the higher concentrations tested (up to 25µM), apoptosis was the major contributor to the observed cell death, and that was associated with JNK activation. Using the JNK inhibitor SP600125 and the pan-caspase inhibitor z-VAD, apoptosis induced by the extracts/compounds was shown to be dependent on JNK and caspases activation. At intermediate concentrations of extracts/compounds, a delayed and non-apoptotic type of cell death was present, which was associated with a significant activation of AMPK and a decrease of p53 levels. Altogether, these results demonstrate that the wasted bark of E. nitens can be used as a potential source of interesting cytotoxic natural triterpenoids against cancer cells.GEORG THIEME VERLAG KG2017-12-07T19:54:58Z2014-01-01T00:00:00Z2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/20659eng0032-094310.1055/s-0034-1394854Calcada, C.Pereira, J.Domingues, R. M. A.Silvestre, A. J. D.Duarte, F.Pereira-Wilson, C.Lima, C. F.info: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:RCAAP2024-05-06T04:09:28Zoai:ria.ua.pt:10773/20659Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-06T04:09:28Repositório 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 Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
title Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
spellingShingle Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
Calcada, C.
Eucalyptus nitens
bark extracts
triterpenoids
HCT116 cancer cells
cytotoxicity
apoptosis
cell cycle arrest
title_short Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
title_full Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
title_fullStr Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
title_full_unstemmed Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
title_sort Cytotoxicity of triterpenoids-enriched extracts from bark of Eucalyptus nitens against colorectal HCT116 cancer cells
author Calcada, C.
author_facet Calcada, C.
Pereira, J.
Domingues, R. M. A.
Silvestre, A. J. D.
Duarte, F.
Pereira-Wilson, C.
Lima, C. F.
author_role author
author2 Pereira, J.
Domingues, R. M. A.
Silvestre, A. J. D.
Duarte, F.
Pereira-Wilson, C.
Lima, C. F.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Calcada, C.
Pereira, J.
Domingues, R. M. A.
Silvestre, A. J. D.
Duarte, F.
Pereira-Wilson, C.
Lima, C. F.
dc.subject.por.fl_str_mv Eucalyptus nitens
bark extracts
triterpenoids
HCT116 cancer cells
cytotoxicity
apoptosis
cell cycle arrest
topic Eucalyptus nitens
bark extracts
triterpenoids
HCT116 cancer cells
cytotoxicity
apoptosis
cell cycle arrest
description Eucalyptus nitens crops are used in Portugal mainly by the pulp and paper industries, producing substantial bark residues with no added value use [1]. They can, however, be an interesting source of bioactive triterpenic compounds. Here, a lipophilic crude extract (CE) from bark of E. nitens prepared with dichloromethane [1] with about 70% (w/w) of triterpenoids, and a fraction of this (F2) more enriched in triterpenoids (93% w/w), as well as their main compounds betulinic acid (BiA) and betulonic acid (BoA), were used to determine their potential cytotoxicity against the colorectal HCT116 cancer cells. After 48h of incubation, the extracts/compounds inhibited significantly cell growth in a concentration-dependent manner (assessed by the MTT assay), with a GI50 s of 1.3 µg/mL and 2.2 µg/mL for F2 and CE extracts, respectively, and of 0.8µM and 3.9µM for BoA and BiA, respectively. The inhibition of cell growth was shown to be dependent on both the arrest of cell cycle at the G2/M phase, and the induction of cell death (assessed by PI staining). At the higher concentrations tested (up to 25µM), apoptosis was the major contributor to the observed cell death, and that was associated with JNK activation. Using the JNK inhibitor SP600125 and the pan-caspase inhibitor z-VAD, apoptosis induced by the extracts/compounds was shown to be dependent on JNK and caspases activation. At intermediate concentrations of extracts/compounds, a delayed and non-apoptotic type of cell death was present, which was associated with a significant activation of AMPK and a decrease of p53 levels. Altogether, these results demonstrate that the wasted bark of E. nitens can be used as a potential source of interesting cytotoxic natural triterpenoids against cancer cells.
publishDate 2014
dc.date.none.fl_str_mv 2014-01-01T00:00:00Z
2014
2017-12-07T19:54:58Z
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/10773/20659
url http://hdl.handle.net/10773/20659
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0032-0943
10.1055/s-0034-1394854
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 GEORG THIEME VERLAG KG
publisher.none.fl_str_mv GEORG THIEME VERLAG KG
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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