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Biochemical, Molecular, and Genetic Mechanisms

Trigonelline Is a Novel Phytoestrogen in Coffee Beans^1,2

³ Department of Nutrition and Food Science and ⁴ Institute for Obesity Research and Program Evaluation, Texas A&M University, College Station, TX 77843; and ⁵ Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523

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 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 (E₂), using proliferation of estrogen-dependent human breast cancer (MCF-7) cells as a model system. When cells were cotreated with suboptimal doses of E₂ (10 pmol/L) and Trig (100 pmol/L), an additive enhancement of MCF-7 growth was observed. In the absence of E₂, 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 E₂. While our data demonstrate that Trig activates the ER, competitive binding assays showed that Trig does not compete E₂ 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.

^* To whom correspondence should be addressed. E-mail:callred{at}tamu.edu.

Manuscript received 28 March 2009. Initial review completed 20 April 2009. Revision accepted 24 July 2009.

Published online 26 August 2009.