Data from 2-Methoxyestradiol Inhibits Barrett's Esophageal Adenocarcinoma Growth and Differentiation through Differential Regulation of the β-Catenin–E-Cadherin Axis

Abstract

<div>Abstract<p>The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME<sub>2</sub>), a promising anticancer agent, modulates Barrett's esophageal adenocarcinoma (BEAC) cell growth and behavior through a cellular pathway involving β-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<sub>2</sub> 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 β-catenin and E-cadherin and binding of these two proteins is activated in a 2-ME<sub>2</sub>–dependent fashion in Bic-1 cells. Moreover, overexpressions of these two proteins may be due to the stabilization of these proteins by 2-ME<sub>2</sub>. We found that 2-ME<sub>2</sub>–induced antimigratory effects are mediated through the β-catenin–E-cadherin signaling pathways. In view of these results, we determined whether 2-ME<sub>2</sub> 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<sub>2</sub> on β-catenin–orchestrated signal transduction plausibly plays a multifaceted functional role to inhibit the proliferation and cell migration of 2-ME<sub>2</sub>–treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett's esophageal adenocarcinoma. Mol Cancer Ther; 9(3); 523–34</p></div>