Comparative Effects of Soy Phytoestrogens and 17β-Estradiol on DNA Methylation of a Panel of 24 Genes in Prostate Cancer Cell Lines

Abstract

Major phytoestrogens genistein and daidzein have been reported to have the ability to reverse DNA methylation in cancer cell lines. The mechanism by which genistein and daidzein have an inhibiting action on DNA methylation is not well understood. The aim of this study was to investigate the effects of soy phytoestrogens and the natural estrogen 17β-estradiol (E₂) to determine whether one of the estrogen receptors is mobilized for the action of these compounds on DNA methylation. We also made a comparative study with a DNA methylation inhibitor (5-azacytidine) and a DNA methylation activator (budesonide). Three prostate cell lines, PC-3, DU-145, and LNCaP, were treated with 40 μM genistein, 110 μM daidzein, 2 μM budesonide, 2 μM 5-azacytidine, and 10 μM E₂. In these 3 human prostate cancer cell lines, we performed methylation quantification using methyl-profiler-DNA-methylation analysis. Soy phytoestrogens and E₂ induced a demethylation of all the promoter regions studied except for those that were unmethylated in control cells. Our results showed that E₂ induces, like soy phytoestrogen, a decrease in DNA methylation in prostate cancer cell lines. This action may be mediated through ERβ.

ACKNOWLEDGMENT

The authors thank Nicolas Sonnier for technical assistance.