The estrogenic effect of trigonelline and 3,3-diindolymethane on cell growth in non-malignant colonocytes

Abstract

Epidemiological and animal data have demonstrated the protective effects of estrogen signaling on colon carcinogenesis. Nonetheless, studies have suggested that estrogen replacement therapy is positively correlated to increased risk of breast cancer. Therefore, there is considerable interest in investigating novel phytoestrogens that mimic the protective actions of estrogen in the colon. Trigonelline (Trig) and 3,3-diindolylmethane (DIM) have been reported as phytoestrogens in spite of their distinct chemical structures from other phytoestrogens. Both compounds elicit estrogenic responses without directly interacting with the binding domain of the estrogen receptor (ER). We examined the influence of Trig and DIM on non-malignant colonocytes. Both compounds reduced cell growth of young adult mouse colonocytes (YAMCs). Trig and DIM induced cell cycle arrest in the G0/G1 phase and enhanced apoptosis in YAMCs. The inhibitory effect of Trig on cell growth was disrupted by co-treatment of ICI 182,780, an ER antagonist. DIM elevated ER mediated transcriptional activity. Both compounds changed gene expression related to apoptosis and cell proliferation in unique ways. In conclusion, Trig and DIM impact cell physiology and gene expression in YAMCs via novel estrogenic actions and these data suggest that intake of novel phytoestrogens may activate protective effects of estrogen signaling in the colon.