Trigonelline Is a Novel Phytoestrogen in Coffee Beans
Trigonelline Is a Novel Phytoestrogen in Coffee Beans
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DOI：
10.3945/jn.109.108001
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Allred, Clinton D.
中科院分区：
文献类型：
--
作者：
Allred, Kimberly F.;Yackley, Katarina M.;Allred, Clinton D.
喝咖啡与几种内分泌相关癌症的发生有关。对这些数据的解释往往局限于咖啡因所起的作用。胡芦巴碱（Trigonelline，Trig）是一种与烟酸相关的化合物，是咖啡的天然成分，约占烘焙咖啡豆干物质的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确定Trig是否改变雌二醇（E-2）的作用，使用雌激素依赖性人乳腺癌（MCF-7）细胞的增殖作为模型系统。当用次优剂量的E-2（10 pmol/L）和Trig（100 pmol/L）共处理细胞时，观察到MCF-7生长的累加增强。在缺乏E-2的情况下，Trig以剂量响应方式刺激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，抑制Trig诱导的细胞增殖。Trig处理还诱导MCF-7细胞中雌激素反应元件报告基因测定的激活，并增加ER靶基因（pS2、孕酮受体和细胞周期蛋白D1）的表达，类似于E-2。虽然我们的数据表明Trig激活ER，但竞争性结合测定显示Trig在任何浓度下都不竞争E-2脱离ER。这表明Trig通过一种单独的机制激活ER。总的来说，这些数据表明，Trig即使在低浓度下也能刺激MCF-7细胞生长，并且这种作用是通过ER介导的，清楚地将Trig鉴定为新型植物雌激素。J.营养139：1833-1838，2009.
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 similar to 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. J. Nutr. 139: 1833-1838, 2009.