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Neutral oligosaccharides from human milk induces G2/M growth arrest in intestinal epithelial cells
Author(s) -
Kuntz Sabine,
Rudloff Silvia,
Kunz Clemens
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a154-c
Subject(s) - cell cycle , cell growth , apoptosis , cyclin d2 , cell cycle checkpoint , microbiology and biotechnology , cyclin b1 , biology , cyclin , cyclin a , chemistry , biochemistry , cyclin dependent kinase 1
Lactose‐derived oligosaccharides are the third most abundant constituents of human milk and are thought to be associated with many benefits for the breast‐fed infant, although information about their effects on intestinal cell dynamic processes is rare. Therefore, we investigated proliferation, differentiation and apoptosis in intestinal cell lines. In addition, the role of cell cycle genes during cell cycle arrest was determined by real time PCR. mRNA expression correlated with growth associated events. HT‐29 cells were exposed to 7.5 and 15 mg/mL neutral oligosaccharides. These oligosaccharides decreased intestinal cell proliferation in HT‐29 cells dose‐dependently with only a slight induction of alkaline phosphate activity (121.26 ± 5.84 %). A pronounced enhancement of caspase‐3 activity (242.45 ± 7.41 %) as a marker of apoptosis was found. In contrast, Caco‐2 cells displayed a dose‐dependent inhibition of growth with failure of induction of differentiation or apoptosis. Cell cycle analysis of HT‐29 cells after 24 h with exposure to neutral oligosaccharides (15 mg/mL) revealed 37 % of cells in G0/G1 and 35 % in G2/M vs. 71 % in G0/G1 and 17 % in G2/M for the control. This G2/M arrest was associated with changes in mRNA expression of cell cycle dependent genes such cyclin A, B, whereas cyclin D and E were ineffective. A G2/M arrest with concomitant cell cycle genes expression can also be observed in HIEC and Caco‐2 cells. Thus, neutral oligosaccharides inhibited intestinal cell proliferation and altered cell cycle dynamics and regulator genes with molecular evidence.