Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves
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/10316/101589 https://doi.org/10.1016/j.arabjc.2015.11.014 |
Resumo: | The hepatocellular carcinoma, a primary malignancy of the liver, has a very poor prognosis and a lower survival rate. Moreover, the inefficacy of conventional therapies emphasizes the importance of discovering new bioactive compounds. Several studies clearly state that plant-derived polyphenols, namely ellagitannins, have several health benefits. Fragaria vesca leaves contain high amounts of polyphenols, being especially rich in ellagitannins. Therefore, this study aimed to characterize an ellagitannin-enriched fraction (EEF) from F. vesca leaves and to unveil the anticancer potential of this fraction on human hepatocellular carcinoma cells. The analysis of EEF by HPLC-PDA-ESI/MSn allowed the detection of 12 ellagitannins. The cell viability of both EEF and crude extract was determined after 24 h of cells treatment and the halfmaximal inhibitory concentration (IC50) was evaluated. The IC50 of the EEF (113 lg/mL) was about 6 times lower than the IC50 of the crude extract (690 lg/mL). Furthermore, EEF induced cell cycle arrest at G2/M checkpoint and decreased cell proliferation in a dose-dependent way. This fraction also induced an accumulation of LC3-II protein through blockage of autophagic flux, and inhibited chymotrypsin-like activity of 26S proteasome. These results showed, for the first time, that EEF from F. vesca leaves inhibits both, autophagic and ubiquitin-proteasome system pathways, two main intracellular protein degradation systems that are targets for anticancer therapies. Additionally, a proteomic analysis allowed the identification of 914 proteins, among which 133 were modulated after cells treatment with EEF, most of them related to metabolic pathways. Overall, this study shows that the EEF from F. vesca leaves decreased cell proliferation, inhibited the proteolytic mechanisms and modulated the metabolic pathways of the cell. Additionally this study points out F. vesca as a source of valuable molecules with anticancer potential, suggesting that ellagitannins, the polyphenols identified in this fraction, could be useful in the development of new fine-tuned therapeutic strategies against carcinogenesis. |
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Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leavesCancerHepG2Proteolytic pathwaysProteomeCell proliferationCell cycleThe hepatocellular carcinoma, a primary malignancy of the liver, has a very poor prognosis and a lower survival rate. Moreover, the inefficacy of conventional therapies emphasizes the importance of discovering new bioactive compounds. Several studies clearly state that plant-derived polyphenols, namely ellagitannins, have several health benefits. Fragaria vesca leaves contain high amounts of polyphenols, being especially rich in ellagitannins. Therefore, this study aimed to characterize an ellagitannin-enriched fraction (EEF) from F. vesca leaves and to unveil the anticancer potential of this fraction on human hepatocellular carcinoma cells. The analysis of EEF by HPLC-PDA-ESI/MSn allowed the detection of 12 ellagitannins. The cell viability of both EEF and crude extract was determined after 24 h of cells treatment and the halfmaximal inhibitory concentration (IC50) was evaluated. The IC50 of the EEF (113 lg/mL) was about 6 times lower than the IC50 of the crude extract (690 lg/mL). Furthermore, EEF induced cell cycle arrest at G2/M checkpoint and decreased cell proliferation in a dose-dependent way. This fraction also induced an accumulation of LC3-II protein through blockage of autophagic flux, and inhibited chymotrypsin-like activity of 26S proteasome. These results showed, for the first time, that EEF from F. vesca leaves inhibits both, autophagic and ubiquitin-proteasome system pathways, two main intracellular protein degradation systems that are targets for anticancer therapies. Additionally, a proteomic analysis allowed the identification of 914 proteins, among which 133 were modulated after cells treatment with EEF, most of them related to metabolic pathways. Overall, this study shows that the EEF from F. vesca leaves decreased cell proliferation, inhibited the proteolytic mechanisms and modulated the metabolic pathways of the cell. Additionally this study points out F. vesca as a source of valuable molecules with anticancer potential, suggesting that ellagitannins, the polyphenols identified in this fraction, could be useful in the development of new fine-tuned therapeutic strategies against carcinogenesis.2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/101589http://hdl.handle.net/10316/101589https://doi.org/10.1016/j.arabjc.2015.11.014eng18785352Liberal, JoanaCosta, GustavoCarmo, AnáliaVitorino, RuiMarques, CarlaDomingues, Maria RosárioDomingues, Pedro Mariano MotaGonçalves, Ana CristinaAlves, RaquelSarmento-Ribeiro, Ana BelaGirão, HenriqueCruz, Maria TeresaBatista, Maria Teresainfo: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:RCAAP2022-09-01T20:46:23Zoai:estudogeral.uc.pt:10316/101589Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:18:44.969439Repositório 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 |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
title |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
spellingShingle |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves Liberal, Joana Cancer HepG2 Proteolytic pathways Proteome Cell proliferation Cell cycle |
title_short |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
title_full |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
title_fullStr |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
title_full_unstemmed |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
title_sort |
Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves |
author |
Liberal, Joana |
author_facet |
Liberal, Joana Costa, Gustavo Carmo, Anália Vitorino, Rui Marques, Carla Domingues, Maria Rosário Domingues, Pedro Mariano Mota Gonçalves, Ana Cristina Alves, Raquel Sarmento-Ribeiro, Ana Bela Girão, Henrique Cruz, Maria Teresa Batista, Maria Teresa |
author_role |
author |
author2 |
Costa, Gustavo Carmo, Anália Vitorino, Rui Marques, Carla Domingues, Maria Rosário Domingues, Pedro Mariano Mota Gonçalves, Ana Cristina Alves, Raquel Sarmento-Ribeiro, Ana Bela Girão, Henrique Cruz, Maria Teresa Batista, Maria Teresa |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Liberal, Joana Costa, Gustavo Carmo, Anália Vitorino, Rui Marques, Carla Domingues, Maria Rosário Domingues, Pedro Mariano Mota Gonçalves, Ana Cristina Alves, Raquel Sarmento-Ribeiro, Ana Bela Girão, Henrique Cruz, Maria Teresa Batista, Maria Teresa |
dc.subject.por.fl_str_mv |
Cancer HepG2 Proteolytic pathways Proteome Cell proliferation Cell cycle |
topic |
Cancer HepG2 Proteolytic pathways Proteome Cell proliferation Cell cycle |
description |
The hepatocellular carcinoma, a primary malignancy of the liver, has a very poor prognosis and a lower survival rate. Moreover, the inefficacy of conventional therapies emphasizes the importance of discovering new bioactive compounds. Several studies clearly state that plant-derived polyphenols, namely ellagitannins, have several health benefits. Fragaria vesca leaves contain high amounts of polyphenols, being especially rich in ellagitannins. Therefore, this study aimed to characterize an ellagitannin-enriched fraction (EEF) from F. vesca leaves and to unveil the anticancer potential of this fraction on human hepatocellular carcinoma cells. The analysis of EEF by HPLC-PDA-ESI/MSn allowed the detection of 12 ellagitannins. The cell viability of both EEF and crude extract was determined after 24 h of cells treatment and the halfmaximal inhibitory concentration (IC50) was evaluated. The IC50 of the EEF (113 lg/mL) was about 6 times lower than the IC50 of the crude extract (690 lg/mL). Furthermore, EEF induced cell cycle arrest at G2/M checkpoint and decreased cell proliferation in a dose-dependent way. This fraction also induced an accumulation of LC3-II protein through blockage of autophagic flux, and inhibited chymotrypsin-like activity of 26S proteasome. These results showed, for the first time, that EEF from F. vesca leaves inhibits both, autophagic and ubiquitin-proteasome system pathways, two main intracellular protein degradation systems that are targets for anticancer therapies. Additionally, a proteomic analysis allowed the identification of 914 proteins, among which 133 were modulated after cells treatment with EEF, most of them related to metabolic pathways. Overall, this study shows that the EEF from F. vesca leaves decreased cell proliferation, inhibited the proteolytic mechanisms and modulated the metabolic pathways of the cell. Additionally this study points out F. vesca as a source of valuable molecules with anticancer potential, suggesting that ellagitannins, the polyphenols identified in this fraction, could be useful in the development of new fine-tuned therapeutic strategies against carcinogenesis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 |
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/10316/101589 http://hdl.handle.net/10316/101589 https://doi.org/10.1016/j.arabjc.2015.11.014 |
url |
http://hdl.handle.net/10316/101589 https://doi.org/10.1016/j.arabjc.2015.11.014 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
18785352 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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 |
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 |
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1799134082191327232 |