In
prostate cancer, DNA methylation is significantly associated with
tumor initiation, progression, and
metastasis. Previous studies have suggested that soy
phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for
prostate cancer. The purpose of our study was to examine the modulation effects of
phytoestrogens on a genome-wide scale in regards to DNA methylation in
prostate cancer.
Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of
genistein and 110 μM of
daidzein. DNMT inhibitor
5-azacytidine (2 μM) and the methylating agent
budesonide (2 μM) were used to compare their demethylation/methylation effects with
phytoestrogens. The regulatory effects of
phytoestrogens on DNA methylation were analyzed by using a methyl-
DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by
genistein and
daidzein treatments in DU-145 and LNCaP
prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by
genistein treatment. Our results suggest that the modulation effects of
phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of
prostate cancer.