S-equol inhibits proliferation and promotes apoptosis of human breast cancer MCF-7 cells via regulating miR-10a-5p and PI3K/AKT pathway

Arch Biochem Biophys. 2019 Sep 15;672:108064. doi: 10.1016/j.abb.2019.108064. Epub 2019 Aug 4.

Abstract

S-equol is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, which has strong anti-cancer activity. Based on this, the purpose of this study was to investigate the anti-breast cancer mechanism of S-equol. We examined the effects of S-equol on proliferation and apoptosis of MCF-7 cells by cell counting kit-8 assay and flow cytometry. Screening for microRNAs and predicting their target genes using the starBase and Targetscan website, respectively. Protein expression was detected by Western blot. The microRNA level were quantified by real-time PCR. The results showed that S-equol inhibited the proliferation of breast cancer MCF-7 cells in a time- and dose-dependent manner and promoted apoptosis of MCF-7 cells. The expression of miR-10a-5p was significantly decreased in breast cancer tissues and breast cancer cell lines, and the expression of miR-10a-5p was negatively correlated with the proliferation of MCF-7 cells. Luciferase reporter experiments demonstrated that miR-10a-5p directly targets PIK3CA 3'UTR to function. It was further found that S-equol exerts an anti-breast cancer effect by up-regulating miR-10a-5p and inhibiting the PI3K/AKT pathway. Our study revealed the mechanism of S-equol against breast cancer, and miR-10a-5p may be a potential target for the treatment of breast cancer.

Keywords: Breast cancer; MCF-7; PI3K/AKT; S-Equol; miR-10a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects*
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Equol / chemistry
  • Equol / pharmacology*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Stereoisomerism

Substances

  • MIRN10 microRNA, human
  • MicroRNAs
  • Equol
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt