DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines.
Summary of "DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines."
Aim: 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 & materials: 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. Conclusion: 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.
Département d'Oncogénétique, Centre Jean Perrin, 58 rue Montalembert, 63001 Clermont-Ferrand, Cedex 01, France.
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Medical and Biotech [MESH] Definitions
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Prostatic Secretory Proteins
Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.
A family of trypsin-like SERINE ENDOPEPTIDASES that are expressed in a variety of cell types including human prostate epithelial cells. They are formed from tissue prokallikrein by action with TRYPSIN. They are highly similar to PROSTATE-SPECIFIC ANTIGEN. EC 126.96.36.199.
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Ultrasound, High-intensity Focused, Transrectal
Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).
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