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: Agnieszka Bielecki, Jennifer Roberts, Rekha Mehta, Jayadev Raju
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 63 Issue 1 Pg. 139-50 ( 2011) ISSN: 1532-7914 [Electronic] United States
• PMID: 21161820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Estrogen Receptor beta
• Isoflavones
• NF-kappa B
• daidzein
• glycitein
• Genistein

Topics

• Adenocarcinoma (prevention & control)
• Anticarcinogenic Agents (pharmacology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Colonic Neoplasms (prevention & control)
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis)
• Estrogen Receptor beta (antagonists & inhibitors, genetics, physiology)
• Genistein (pharmacology)
• Humans
• Isoflavones (pharmacology)
• NF-kappa B (antagonists & inhibitors)