Abstract 3712: 2-Methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and aggressive phenotypes through differential regulation of β-catenin-E-cadherin-axis

Abstract

Abstract The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME2), a promising anticancer agent, modulates Barrett's esophageal adenocarcinoma (BEAC) cell growth and behavior through cellular pathway involving beta-catenin in partnership with E-cadherin, which appears to play a critical role in the induction of antitumor responses in cancer cells. We found that 2-ME2 markedly reduced the BEAC cell proliferation via 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-ME2-dependent fashion in Bic-1 cells. Moreover, over expressions of these two proteins may be due to the stabilization of these proteins by 2-ME2. We found that 2-ME2-induced anti-migratory effects are mediated through the beta-catenin -E-cadherin signaling pathways. In view of these results, we determined whether 2-ME2 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 impact of 2-ME2 on beta-catenin-orchestrated signal transduction plausibly plays a multi-faceted functional role to inhibit the proliferation and cell migration of 2-ME2 treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett's esophageal adenocarcinoma Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3712.