Anthocyanin‑rich blackcurrant extract inhibits proliferation of the MCF10A healthy human breast epithelial cell line through induction of G0/G1 arrest and apoptosis

Mol Med Rep. 2017 Nov;16(5):6134-6141. doi: 10.3892/mmr.2017.7391. Epub 2017 Aug 29.

Abstract

Blackcurrants (Ribes nigrum L., Grossulariaceae) possess a high content of anthocyanin polyphenols, which have been demonstrated to exhibit beneficial effects on health due to their antioxidant and anticarcinogenic prope-rties. The present study investigated novel functions of anthocyanin‑rich blackcurrant extracts (BCEs) in a healthy mammary epithelial cell line, MCF10A. The percentages of viable cells were 85, 75, 53 and 31% following exposure to 50, 100, 200 and 400 µg/ml BCE, respectively. The half‑maximal response concentration of BCE was 237.7 µg/ml. Microarray and Ingenuity® Pathway Analysis demonstrated that BCE downregulated cell cycle signaling, including upstream genes with mitotic roles such as polo‑like kinase signaling. BCE increased the number of cells in the G0/G1 phase and decreased the number of cells in the S and G2/M phases. Alkaline comet assays demonstrated that 50 and 100 µg/ml BCE induced DNA damage in a dose‑dependent manner. Cultures treated with 0, 50, and 100 µg/ml BCE contained 4.6, 13.4 and 16.0% apoptotic cells, respectively. As compared with the untreated cultures (1.9%), the number of necrotic cells increased in the 100 µg/ml BCE‑treated cultures (from 1.9 to 4.3%) but not in the 50 µg/ml BCE‑treated cultures. Reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that BCE reduced mRNA expression of the genomic caretaker lysine‑specific demethylas 5B (KDM5B). The results suggested that blackcurrant anthocyanins may act as cell arrest and death inducers via KDM5B downregulation in healthy breast cells.

MeSH terms

  • Anthocyanins / pharmacology*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Breast / drug effects*
  • Breast / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cell Proliferation / drug effects*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • G1 Phase / drug effects*
  • Humans
  • Nuclear Proteins / metabolism
  • Plant Extracts / pharmacology
  • Polyphenols / pharmacology
  • Resting Phase, Cell Cycle / drug effects*
  • Ribes / chemistry
  • Signal Transduction / drug effects

Substances

  • Anthocyanins
  • Antioxidants
  • Nuclear Proteins
  • Plant Extracts
  • Polyphenols