Centre Jean Perrin, Département d'Oncogénétique, CBRV, 28 Place Henri Dunant, Clermont-Ferrand, France.
Br J Nutr. 2012 Oct;108(7):1187-93. doi: 10.1017/S000711451100657X. Epub 2012 Jan 5.
S-Equol is a metabolite resulting from the conversion of daidzein, a soya phyto-oestrogen, by the gut microflora. The potential protective effects of equol in breast cancer are still under debate. Consequently, we investigated the effects of equol on DNA methylation of breast cancer susceptibility genes (BRCA1 and BRCA2) and oncosuppressors in breast cancer cell lines (MDA-MB-231 and MCF-7) and in a dystrophic breast cell line (MCF-10a) following exposure to S-equol (2 μm) for 3 weeks. We demonstrated by quantitative analysis of methylated alleles a significant decrease in the methylation of the cytosine phosphate guanine (CpG) islands in the promoters of BRCA1 and BRCA2 after the S-equol treatment in MCF-7 and MDA-MB-231 cells and a trend in MCF-10a cells. We also showed that S-equol increases BRCA1 and BRCA2 protein expression in the nuclei and the cytoplasm in MCF-7, MDA-MB-231 and MCF-10a cell lines by immunohistochemistry. The increase in BRCA1 and BRCA2 proteins was also found after Western blotting in the studied cell lines. In summary, we demonstrated the demethylating effect of S-equol on the CpG islands inside the promoters of BRCA1 and BRCA2 genes, resulting in an increase in the level of expressed oncosuppressors in breast cancer cell lines.
S-Equol 是大豆异黄酮的肠道微生物代谢物，大豆异黄酮是一种植物雌激素。Equol 对乳腺癌的潜在保护作用仍存在争议。因此，我们研究了 S-Equol（2μm）处理 3 周后，对乳腺癌易感基因（BRCA1 和 BRCA2）和乳腺癌细胞系（MDA-MB-231 和 MCF-7）以及营养不良乳腺细胞系（MCF-10a）中的乳腺癌细胞系中的 BRCA1 和 BRCA2 基因的 DNA 甲基化和抑癌基因的影响。我们通过定量分析甲基化等位基因，证明 S-Equol 处理后 MCF-7 和 MDA-MB-231 细胞中 BRCA1 和 BRCA2 启动子中的胞嘧啶磷酸鸟嘌呤（CpG）岛的甲基化显著降低，MCF-10a 细胞中存在趋势。我们还表明，S-Equol 通过免疫组织化学法增加 MCF-7、MDA-MB-231 和 MCF-10a 细胞系中 BRCA1 和 BRCA2 蛋白在核和细胞质中的表达。Western blot 也显示在研究的细胞系中 BRCA1 和 BRCA2 蛋白的增加。总之，我们证明了 S-Equol 对 BRCA1 和 BRCA2 基因启动子内 CpG 岛的去甲基化作用，导致乳腺癌细胞系中抑癌基因表达水平的增加。
