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

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 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 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 β-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 β-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 β-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. Mol Cancer Ther; 9(3); 523-34. ©2010 AACR.

Effects of Parafibromin Expression on the Phenotypes and Relevant Mechanisms in the DLD-1 Colon Carcinoma Cell Line

“…Additionally, our in vitro experiment showed that forced parafibromin overexpression caused the differentiation of carcinoma cells evidenced by enhanced ALP activity and regular appearance. Although both differentiation markers (E-cahderin and β-catenin) were examined by western blot and immunofluorescence (Kambhampati et al, 2010), we found no difference in their expression between both cells, indicating the parafibromin-induced differentiation might be independent of both cells adherent molecules in DLD-1 cells.…”

The Matricellular Protein CCN1/Cyr61 Is a Critical Regulator of Sonic Hedgehog in Pancreatic Carcinogenesis

“…SP and Non-SP) were briefly cultured in DMEM with 10% FCS in 5% CO 2 at 37°C, and then cells (5 ϫ 10 4 cells suspended in Matrigel to a final volume of 100 l) were injected s.c. into the right rear flank of 6 -8-week-old male athymic nude mice (6 mice per group) and tumor growth was monitored starting after the 2nd day of injection. This was continued for up to 45 days or more using our previous methods (32,33). Male athymic nude mice (nu/nu genotype) were obtained from Charles Rivers (Wilmington, MA) and acclimated to our facility for 1 week before starting the experiments.…”

A Second-Generation 2-Methoxyestradiol Prodrug Is Effective against Barrett's Adenocarcinoma in a Mouse Xenograft Model

“…OE33-tumor xenografts were generated essentially as previously described (20, 21). Briefly, semiconfluent OE33 cells (2.5×10 6 ) were re-suspended in Matrigel and were injected sc into the right hind leg of each mouse for the development of the tumor.…”

“…The immunofluorescence procedure was the same as previously described (21, 22). Briefly, for in vitro analysis, OE33 cells were fixed with acetone and permeabilized with 0.1% Triton X-100.…”