Abstract
B114
We have previously demonstrated that soy isoflavones elicit a colon cancer preventive effect when exposed throughout the lifetime of rats, inclusive of in utero and post-natal stages using an experimental model. We also showed that soy isoflavones increased the expression of colon tumor estrogen receptor (ER)-β, one of the main candidates in endocrine disruption during colon carcinogenesis. To further understand the relationship between the role of soy isoflavones and ER-β in colon carcinogenesis, we examined the effects of soy isoflavones in DLD-1 human colon adenocarcinoma cells in the presence of ER-β or when expression was decreased by RNA interference (siRNA) in vitro. DLD-1 cells were treated with increasing concentrations of soy isoflavones composed of genistein, daidzein and glycitein at a ratio of 1:1:0.2 representing human soy isoflavone-rich food intake. Markers of cell signaling were determined following treatment with or without soy isoflavones in the presence or absence of ER-β gene silencing. Soy isoflavones inhibited the growth of DLD-1 cells dose dependently, with an IC50 for cytotoxicity at 24.82 µg/mL and an IC50 for cell viability at 17.01 µg/mL. At sub-cytotoxic doses, soy isoflavones modulated the expression of markers associated with MAP kinase, AKT and NFκB signalling pathways, cell proliferation and cell cycle regulation, all conducive to a growth restrictive effect. A 75% knockdown of ER-β at the gene and protein level was achieved in DLD-1 cells using siRNA, and this caused a differential expression of the molecular markers studied above. Our results suggest that ER-β appears crucial in mediating the growth suppressive effects of soy isoflavones. ER-β may play an important role in the action of several endocrine disruptors including food chemical contaminants during colon carcinogenesis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B114.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC
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