title: 2-methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and differentiation through differential regulation of the beta-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 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.
authors.affiliation: Cancer Research Unit, Research Division 151, VA Medical Center, Kansas City, Missouri 64128, USA. skambhampati@kumc.edu
authors.forename: Suman
authors.initials: S
authors.lastname: Kambhampati
authors.forename: Snigdha
authors.initials: S
authors.lastname: Banerjee
authors.forename: Kakali
authors.initials: K
authors.lastname: Dhar
authors.forename: Smita
authors.initials: S
authors.lastname: Mehta
authors.forename: Inamul
authors.initials: I
authors.lastname: Haque
authors.forename: Gopal
authors.initials: G
authors.lastname: Dhar
authors.forename: Monami
authors.initials: M
authors.lastname: Majumder
authors.forename: Gibanananda
authors.initials: G
authors.lastname: Ray
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Vanveldhuizen
authors.forename: Sushanta K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000077584:2-Methoxyestradiol; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D051176:beta Catenin; D004958:Estradiol; D000077584:2-Methoxyestradiol