Effect of daidzein and equol on DNA replication in MCF-7 cells

J Biochem. 2018 May 1;163(5):371-380. doi: 10.1093/jb/mvy006.

Abstract

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.

MeSH terms

  • Cell Cycle Proteins / metabolism
  • DNA Replication / drug effects*
  • DNA, Neoplasm / drug effects*
  • DNA, Neoplasm / metabolism
  • Equol / pharmacology*
  • Humans
  • Isoflavones / pharmacology*
  • MCF-7 Cells
  • Minichromosome Maintenance Complex Component 2 / metabolism
  • Minichromosome Maintenance Complex Component 3 / metabolism
  • Minichromosome Maintenance Complex Component 4 / metabolism
  • Minichromosome Maintenance Complex Component 6 / metabolism
  • Minichromosome Maintenance Complex Component 7 / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / metabolism

Substances

  • Cell Cycle Proteins
  • DNA, Neoplasm
  • Isoflavones
  • MCM3 protein, human
  • MCM5 protein, human
  • RNA, Messenger
  • Equol
  • daidzein
  • MCM2 protein, human
  • MCM4 protein, human
  • MCM6 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 3
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7