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Title: Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves
Authors: 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 
Keywords: Cancer; HepG2; Proteolytic pathways; Proteome; Cell proliferation; Cell cycle
Issue Date: 2019
Project: FEDER/COMPETE (FCOMP-01-0124- FEDER-011096) 
PEst-C/SAU/ LA0001/2013-2014 
QOPNA research unit (project PEst-C/QUI/UI0062/2013; FCOMP-01-0124- FEDER-037296) 
Serial title, monograph or event: Arabian Journal of Chemistry
Volume: 12
Issue: 8
Abstract: 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.
ISSN: 18785352
DOI: 10.1016/j.arabjc.2015.11.014
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
I&D CIBIT - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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