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

Nanashima,Naoki; Horie,Kayo; Chiba,Mitsuru; Nakano,Manabu; Maeda,Hayato; Nakamura,Toshiya

doi:10.3892/mmr.2017.7391

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

Authors:
- Naoki Nanashima
- Kayo Horie
- Mitsuru Chiba
- Manabu Nakano
- Hayato Maeda
- Toshiya Nakamura
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Affiliations: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Aomori 036‑8561, Japan
Published online on: August 29, 2017 https://doi.org/10.3892/mmr.2017.7391
Pages: 6134-6141

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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 properties. 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.

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