Ibaraki University, Mito, Ibaraki 310-8512, Japan.
National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo 162-8636, Japan.
J Biochem. 2018 May 1;163(5):371-380. doi: 10.1093/jb/mvy006.
It has been reported that daidzein and equol stimulate DNA replication and proliferation of MCF-7 cells. However, their molecular mechanisms of action are still unclear. We examined the effects of daidzein and equol on DNA replication of MCF-7 cells, focusing on MCM2-7 proteins, which function as the replicative helicase. In the presence of either 1 μM of daidzein or equol, the number of cells in S-phase, which was determined by detecting bromodeoxyuridine incorporated into replicated DNA, almost doubled. The total amounts of MCM7 protein and chromatin-bound MCM7 protein increased in the presence of daidzein. The data suggest that phytoestrogens facilitate cell cycle progression in G1-phase by increasing the level of MCM proteins. In the presence of phytoestrogens, phosphorylation of Rb and levels of MCM2, 3 and 7 mRNA increased, suggesting that stimulation of MCM2-7 transcription is involved in the cell cycle progression. Under the same conditions, double-stranded DNA breakage in logarithmically growing MCF-7 cells, which was detected using anti-γ-H2AX antibodies, did not increase in the presence of equol.
据报道，大豆黄酮和雌马酚可刺激 MCF-7 细胞的 DNA 复制和增殖。然而，其作用机制尚不清楚。我们研究了大豆黄酮和雌马酚对 MCF-7 细胞 DNA 复制的影响，重点研究了作为复制解旋酶的 MCM2-7 蛋白。在 1 μM 的大豆黄酮或雌马酚存在的情况下，通过检测掺入复制 DNA 的溴脱氧尿苷，S 期细胞数量几乎翻了一番。在大豆黄酮存在的情况下，MCM7 蛋白的总量和染色质结合的 MCM7 蛋白增加。数据表明，植物雌激素通过增加 MCM 蛋白的水平促进 G1 期细胞周期进程。在植物雌激素存在的情况下，Rb 的磷酸化和 MCM2、3 和 7 mRNA 的水平增加，表明 MCM2-7 转录的刺激参与细胞周期进程。在相同条件下，用抗 γ-H2AX 抗体检测到，在雌马酚存在的情况下，对数生长期 MCF-7 细胞中的双链 DNA 断裂没有增加。
