title: Estrogen receptor-β mediates the inhibition of DLD-1 human colon adenocarcinoma cells by soy isoflavones.
abstract: To understand the relationship between the role of soy isoflavones and estrogen receptor (ER)-β in colon tumorigenesis, we investigated the cellular effects of soy isoflavones (composed of genistein, daidzein, and glycitein) in DLD-1 human colon adenocarcinoma cells with or without ER-β gene silencing by RNA interference (RNAi). Soy isoflavones decreased the expression of proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase (ERK)-1/2, AKT, and nuclear factor (NF)-κB. Soy isoflavones dose-dependently caused G2/M cell cycle arrest and downregulated the expression of cyclin A. This was associated with inhibition of cyclin dependent kinase (CDK)-4 and up-regulation of its inhibitor p21(cip1) expressions. ER-β gene silencing lowered soy isoflavone-mediated suppression of cell viability and proliferation. ERK-1/2 and AKT expressions were unaltered and NF-κB was modestly upregulated by soy isoflavones after transient knockdown of ER-β expression. Soy isoflavone-mediated arrest of cells at G2/M phase and upregulation of p21(cip1) expression were not observed when ER-β gene was silenced. These findings suggest that maintaining the expression of ER-β is crucial in mediating the growth-suppressive effects of soy isoflavones against colon tumors. Thus upregulation of ER-β status by specific food-borne ER-ligands such as soy isoflavones could potentially be a dietary prevention or therapeutic strategy for colon cancer.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bielecki
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roberts
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
authors.forename: Jayadev
authors.initials: J
authors.lastname: Raju
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors
chemical_list: D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047629:Estrogen Receptor beta; D007529:Isoflavones; D016328:NF-kappa B; C004742:daidzein; C086566:glycitein; D019833:Genistein