Trigonelline and 3,3‐diindolymethane regulate cell growth in non‐malignant colonocytes via estrogen signaling (1045.21)

Abstract

Epidemiological and clinical data suggest that estrogen exposure reduces the incidence of colorectal cancer. However, use of traditional hormone replacement therapy containing estradiol is controversial as it is associated with an elevated incidence of breast cancer. As such, there is considerable interest in identifying novel, plant‐derived, phytoestrogens that can mimic the protective actions of estrogen in the colon. Trigonelline (Trig) and 3,3‐diindolylmethane (DIM) are phytoestrogens which have distinct chemical structures compared to other well described phytoestrogens and both compounds have been reported to elicit estrogenic responses without directly interacting with the binding domain of the estrogen receptor (ER). In this study, we evaluated the ability of these compounds to influence non‐malignant colonocytes in vitro which we have demonstrated is predictive of chemopreventative effects in vivo. Both Trig and DIM suppressed cell growth of young adult mouse colonocytes (YAMCs). Likewise, Trig and DIM disrupted cell cycle progression in the G0/G1 phase and Trig induced programmed cell death. Co‐treatment with ICI 182,780, an ER antagonist, inhibited the effects of Trig but not DIM. Interestingly, DIM did induce transcriptional activity of the ER. In addition, both compounds altered gene expression associated with apoptosis and cell proliferation in unique ways. In conclusion, Trig and DIM alter cell physiology and gene expression in YAMCs via unique estrogenic actions and these data suggest that consumption of these dietary compounds may reduce risk of colon cancer development.