Casein phosphopeptides modulate proliferation and apoptosis in HT-29 cell line through their interaction with voltage-operated L-type calcium channels

被引:64
作者
Perego, Silvia [1 ]
Cosentino, Stefania [1 ]
Fiorilli, Amelia [1 ]
Tettamanti, Guido [1 ,2 ]
Ferraretto, Anita [1 ]
机构
[1] Univ Milan, Dipartimento Chim Biochim & Biotecnol Med, Milan, Italy
[2] IRCCS Policlin San Donato, Milan, Italy
关键词
Casein phosphopeptides; Intestinal cells; Calcium; Depolarization; Calcium channels; Cell cycle; SENSING RECEPTOR; CA2+ ENTRY; TRANSPORT; COLON; PEPTIDES; MECHANISMS; INHIBITION; INDICATORS; PROMOTION; INTESTINE;
D O I
10.1016/j.jnutbio.2011.04.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
At the intestinal level, proliferation and apoptosis are modulated by the extracellular calcium concentration; thus, dietary calcium may exert a chemoprotective role on normal differentiated intestinal cells, while it may behave as a carcinogenesis promoter in transformed cells. Calcium in milk is associated with casein and casein phosphopeptides (CPPs), hence is preserved from precipitation. CPPs were demonstrated to induce uptake of extracellular calcium ions by in vitro intestinal tumor HT-29 cells but only upon differentiation. Here, the hypothesis that CPPs could differently affect proliferation and apoptosis in undifferentiated and differentiated HT-29 cells through their binding with calcium ions was investigated. Results showed that CPPs protect differentiated intestinal cells from calcium overload toxicity and prevent their apoptosis favoring proliferation while inducing apoptosis in undifferentiated tumor cells. The CPP effect on undifferentiated HT-29 cells, similar to that exerted by ethyleneglycol-O, O'-bis(2-aminoethyl)-N, N. N', N'-tetraacetic acid (EGTA), is presumably due to the ability in binding the extracellular calcium. The effect on differentiated HT-29 cells is coupled to the interaction of CPPs with the voltage-operated L-type calcium channels, known to activate calcium entry into the cells under depolarization and to exert a mitogenic effect: the use of an agonist potentiates the cell response to CPPs, while the antagonists abolish the response to CPPs (36% of examined cells) or reduce both the percentage of responsive cells and the increase of intracellular calcium concentration. Taken together, these results confirm the potentialities of CPPs as nutraceuticals/ functional food and also as modulators of cellular processes connected to the expression of a cancer phenotype. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:808 / 816
页数:9
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