Data/hora: 01/06/2024 17:20:19

Provedor de dados: 	56	
País: 	Brazil	
Título: 	Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway	
Autores: 	Wang,J.; Lu,M.L.; Dai,H.L.; Zhang,S.P.; Wang,H.X.; Wei,N.	
Data: 	2015-03-01	
Ano: 	2015	
Palavras-chave: 	Esculetin; Apoptosis; Hepatocellular carcinoma; Mitochondrial-dependent pathway; Antitumor activity.	
Resumo: 	This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.	
Tipo: 	Info:eu-repo/semantics/article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015000300245	
Editor: 	Associação Brasileira de Divulgação Científica	
Relação: 	10.1590/1414-431x20144074	
Formato: 	text/html	
Fonte: 	Brazilian Journal of Medical and Biological Research  v.48 n.3 2015	
Fonte: 	info:eu-repo/semantics/openAccess