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Artículo

Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice

Piccioni, Flavia ValeriaIcon ; Malvicini, MarianaIcon ; García, Mariana GabrielaIcon ; Rodriguez, Andrés; Atorrasagasti, María CatalinaIcon ; Kippes, Néstor Fabián; Piedra Buena, Ignacio T.; Rizzo, Manglio MiguelIcon ; Bayo Fina, Juan MiguelIcon ; Aquino, Jorge BenjaminIcon ; Viola, Manuela; Passi, Alberto; Alaniz, Laura DanielaIcon ; Mazzolini Rizzo, Guillermo DanielIcon
Fecha de publicación: 03/2012
Editorial: Oxford Univ Press Inc
Revista: Glycobiology
ISSN: 0959-6658
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Medicina Básica

Resumen

Liver cirrhosis is characterized by an excessive accumulation of extracellular matrix components, including hyaluronan (HA). In addition, cirrhosis is considered a pre-neoplastic disease for hepatocellular carcinoma (HCC). Altered HA biosynthesis is associated with cancer progression but its role in HCC is unknown. 4-Methylumbelliferone (4-MU), an orally available agent, is an HA synthesis inhibitor with anticancer properties. In this work, we used an orthotopic Hepa129 HCC model established in fibrotic livers induced by thioacetamide. We evaluated 4-MU effects on HCC cells and hepatic stellate cells (HSCs) in vitro by proliferation, apoptosis and cytotoxicity assays; tumor growth and fibrogenesis were also analyzed in vivo. Our results showed that treatment of HCC cells with 4-MU significantly reduced tumor cell proliferation and induced apoptosis, while primary cultured hepatocytes remained unaffected. 4-MU therapy reduced hepatic and systemic levels of HA. Tumors systemically treated with 4-MU showed the extensive areas of necrosis, inflammatory infiltrate and 2-3-fold reduced number of tumor satellites. No signs of toxicity were observed after 4-MU therapy. Animals treated with 4-MU developed a reduced fibrosis degree compared with controls (F1-2 vs F2-3, respectively). Importantly, 4-MU induced the apoptosis of HSCs in vitro and decreased the amount of activated HSCs in vivo. In conclusion, our results suggest a role for 4-MU as an anticancer agent for HCC associated with advanced fibrosis.
Palabras clave: 4-Methylumbelliferone , Liver Cancer , Liver Fibrosis
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/79589
DOI: https://dx.doi.org/10.1093/glycob/cwr158
URL: https://academic.oup.com/glycob/article/22/3/400/2000144
Colecciones
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Piccioni, Flavia Valeria; Malvicini, Mariana; García, Mariana Gabriela; Rodriguez, Andrés; Atorrasagasti, María Catalina; et al.; Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice; Oxford Univ Press Inc; Glycobiology; 22; 3; 3-2012; 400-410
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