Allred Kimberly F, Yackley Katarina M, Vanamala Jairam, Allred Clinton D
Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
J Nutr. 2009 Oct;139(10):1833-8. doi: 10.3945/jn.109.108001. Epub 2009 Aug 26.
Drinking coffee has been associated with the development of several endocrine-related cancers. The interpretation of these data has often been limited to the role that caffeine plays. Trigonelline (Trig), a niacin-related compound, is a natural constituent of coffee accounting for approximately 1% dry matter in roasted beans. Studies exploring the effects of this bioactive compound on mammalian cells are limited. The initial purpose of our studies was to determine whether Trig alters the actions of estradiol (E(2)), using proliferation of estrogen-dependent human breast cancer (MCF-7) cells as a model system. When cells were cotreated with suboptimal doses of E(2) (10 pmol/L) and Trig (100 pmol/L), an additive enhancement of MCF-7 growth was observed. In the absence of E(2), Trig stimulated MCF-7 cell proliferation in a dose-responsive manner and significantly enhanced cell growth at concentrations as low as 100 pmol/L. Cotreatment of MCF-7 cells with Trig and ICI 182,780, an estrogen receptor (ER) antagonist, inhibited Trig-induced cell proliferation. Trig treatment also induced activation of estrogen response element reporter assays in MCF-7 cells and increased expression of ER target genes (pS2, progesterone receptor, and cyclin D1) similar to E(2). While our data demonstrate that Trig activates the ER, competitive binding assays showed that Trig does not compete E(2) off of the ER at any concentration. This suggests that Trig is activating the ER through a separate mechanism. Collectively, these data demonstrate that Trig even at low concentrations stimulates MCF-7 cell growth and that this effect is mediated through ER, clearly identifying Trig as a novel phytoestrogen.
喝咖啡与几种内分泌相关癌症的发生有关。对这些数据的解释通常局限于咖啡因所起的作用。胡芦巴碱（Trig）是一种与烟酸相关的化合物，是咖啡的天然成分，在烘焙咖啡豆中约占干物质的1%。探索这种生物活性化合物对哺乳动物细胞影响的研究有限。我们研究的最初目的是，以雌激素依赖的人乳腺癌（MCF-7）细胞的增殖作为模型系统，确定Trig是否会改变雌二醇（E₂）的作用。当细胞用次优剂量的E₂（10 pmol/L）和Trig（100 pmol/L）共同处理时，观察到MCF-7生长有相加性增强。在没有E₂的情况下，Trig以剂量反应方式刺激MCF-7细胞增殖，并且在低至100 pmol/L的浓度下显著增强细胞生长。用Trig和雌激素受体（ER）拮抗剂ICI 182,780共同处理MCF-7细胞，可抑制Trig诱导的细胞增殖。Trig处理还诱导了MCF-7细胞中雌激素反应元件报告基因检测的激活，并增加了ER靶基因（pS2、孕激素受体和细胞周期蛋白D1）的表达，类似于E₂。虽然我们的数据表明Trig激活了ER，但竞争性结合试验表明，Trig在任何浓度下都不会将E₂从ER上竞争下来。这表明Trig是通过一种独立的机制激活ER的。总的来说，这些数据表明，即使是低浓度的Trig也能刺激MCF-7细胞生长，并且这种作用是通过ER介导的，从而明确将Trig鉴定为一种新型植物雌激素。
