Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)-mediated tumorigenesis by TSAHC and sorafenib.
Cancer Biol Ther
; 11(3): 330-6, 2011 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-21099346
ABSTRACT
Two separate clinical studies of advanced hepatocarcinoma patients recently reported that the multikinase inhibitor sorafenib (nexavar) could extend survival of the patients only by 2-3 months. We also previously demonstrated that 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) blocks the multilayer growth and migration mediated by TM4SF5, which is highly expressed in approximately 80% of Korean hepatocarcinoma patients. Therefore, we wondered how TSAHC might be different from sorafenib to deal with hepatocarcinoma in terms of the therapeutic characteristics including specificity for TM4SF5. TM4SF5 is previously shown to mediate tumorigenesis through cytosolic p27Kip1-mediated inactivation of RhoA, epithelial-mesenchymal transition, multilayer growth, migration, invasion, and tumor angiogenesis. In this study, TSAHC and two derivatives showed similar antagonistic activities against TM4SF5-mediated signaling and multilayer growth in vitro and anti-tumorigenic activity even in early stages of TM4SF5-mediated tumor formation in nude mice. Meanwhile, sorafenib was only effective much later in tumorigenesis in vivo and affected in vitro proliferation in a TM4SF5-independent manner. Altogether, these observations suggest that TSAHC may be a promising anti-tumorigenic reagent, especially against TM4SF5-mediated hepatocarcinoma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Sulfonamidas
/
Benzenossulfonatos
/
Chalcona
/
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
/
Proteínas de Membrana
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Biol Ther
Assunto da revista:
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2011
Tipo de documento:
Article