2-methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and differentiation through differential regulation of the beta-catenin-E-cadherin axis.
Mol Cancer Ther
; 9(3): 523-34, 2010 Mar.
Article
em En
| MEDLINE
| ID: mdl-20197389
ABSTRACT
The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME(2)), a promising anticancer agent, modulates Barrett's esophageal adenocarcinoma (BEAC) cell growth and behavior through a cellular pathway involving beta-catenin in partnership with E-cadherin, which seems to play a critical role in the induction of antitumor responses in cancer cells. We found that 2-ME(2) markedly reduced the BEAC cell proliferation through regulating apoptotic machinery such as Bcl-2 and Bax. It may nullify the aggressive behavior of the cells by reducing the migratory behavior. Expressions of beta-catenin and E-cadherin and binding of these two proteins is activated in a 2-ME(2)-dependent fashion in Bic-1 cells. Moreover, overexpressions of these two proteins may be due to the stabilization of these proteins by 2-ME(2). We found that 2-ME(2)-induced antimigratory effects are mediated through the beta-catenin-E-cadherin signaling pathways. In view of these results, we determined whether 2-ME(2) reduces BEAC tumor growth. Administration of 2-ME2 significantly decreased the growth of BEAC cells xenografted on the flank of nude mice. The evidence presented points out that the effect of 2-ME(2) on beta-catenin-orchestrated signal transduction plausibly plays a multifaceted functional role to inhibit the proliferation and cell migration of 2-ME(2)-treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett's esophageal adenocarcinoma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esôfago de Barrett
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Neoplasias Esofágicas
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Adenocarcinoma
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Caderinas
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Diferenciação Celular
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Proliferação de Células
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Estradiol
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Beta Catenina
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article