Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
Nutr Cancer. 2011;63(1):139-50. doi: 10.1080/01635581.2010.516867.
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.
为了理解大豆异黄酮与雌激素受体-β（ER-β）在结肠肿瘤发生中的作用关系，我们通过 RNA 干扰（RNAi）技术沉默 DLD-1 人结肠腺癌细胞中的 ER-β 基因，研究了大豆异黄酮（由染料木黄酮、大豆苷元和黄豆黄素组成）的细胞效应。大豆异黄酮降低了增殖细胞核抗原（PCNA）、细胞外信号调节激酶（ERK）-1/2、AKT 和核因子（NF）-κB 的表达。大豆异黄酮呈剂量依赖性地引起 G2/M 细胞周期停滞，并下调细胞周期蛋白 A 的表达。这与细胞周期蛋白依赖性激酶（CDK）-4 的抑制和其抑制剂 p21（cip1）的上调有关。沉默 ER-β 基因降低了大豆异黄酮对细胞活力和增殖的抑制作用。ERK-1/2 和 AKT 的表达在 ER-β 表达短暂敲低后不受影响，而 NF-κB 则被轻度上调。当沉默 ER-β 基因时，大豆异黄酮介导的 G2/M 期细胞阻滞和 p21（cip1）表达上调均未观察到。这些发现表明，维持 ER-β 的表达对于介导大豆异黄酮对结肠肿瘤的生长抑制作用至关重要。因此，通过特定的食物来源 ER 配体（如大豆异黄酮）上调 ER-β 状态可能成为结肠癌的一种饮食预防或治疗策略。
