title: DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines.
abstract: OBJECTIVE
  DNA hypermethylation is an epigenetic mechanism which induces silencing of tumor-suppressor genes in prostate cancer. Many studies have reported that specific components of food plants like soy phytoestrogens may have protective effects against prostate carcinogenesis or progression. Genistein and daidzein, the major phytoestrogens, have been reported to have the ability to reverse DNA hypermethylation in cancer cell lines. The aim of this study was to investigate the potential demethylating effects of these two soy compounds on BRCA1, GSTP1, EPHB2 and BRCA2 promoter genes.
  
  
  METHODS
  Prostate cell lines DU-145 and PC-3 were treated with genistein 40 µM, daidzein 110 µM, budesonide (methylating agent) 2 µM and 5-azacytidine (demethylating agent) 2 µM. In these two human prostate cancer cell lines we performed methylation quantification by using Methyl Profiler DNA methylation analysis. This technique is based on a methylation-specific digestion followed by quantitative PCR. We analyzed the corresponding protein expression by western blotting.
  
  
  RESULTS
  Soy phytoestrogens induced a demethylation of all promoter regions studied except for BRCA2, which is not methylated in control cell lines. An increase in their protein expression was also demonstrated by western blot analysis and corroborated the potential demethylating effect of soy phytoestrogens.
  
  
  CONCLUSIONS
  This study showed that the soy phytoestrogens, genistein and daidzein, induce a decrease of methylation of BRCA1, GSTP1 and EPHB2 promoters. Therefore, soy phytoestrogens may have a protective effect on prostate cancer. However, more studies are needed in order to understand the mechanism by which genistein and daidzein have an inhibiting action on DNA methylation.
authors: Département d'Oncogénétique, Centre Jean Perrin, Clermont-Ferrand, France.
authors: Mawussi
authors: M
authors: Adjakly
authors: Rémy
authors: R
authors: Bosviel
authors: Nadège
authors: N
authors: Rabiau
authors: Jean-Paul
authors: JP
authors: Boiteux
authors: Yves-Jean
authors: YJ
authors: Bignon
authors: Laurent
authors: L
authors: Guy
authors: Dominique
authors: D
authors: Bernard-Gallon
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D048789:Phytoestrogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism*; D036183:Receptor, EphB2 / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D007529:Isoflavones; D048789:Phytoestrogens; C004742:daidzein; D019833:Genistein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D036183:Receptor, EphB2