Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation☆
Received 29 July 2008; received in revised form 16 November 2008; accepted 15 December 2008. published online 15 April 2009.
Abstract
Caseinphosphopeptides (CPPs) are considered as mineral carriers because of their ability to bind and solubilize calcium ions, with the possible role, yet to be definitely assessed, of improving calcium absorption at the intestinal level. Previous works demonstrated that CPPs improve calcium uptake, with increasing intracellular calcium concentration, by human differentiated tumor HT-29 cells, and that this effect correlates with the supramolecular structure of CPPs in the presence of calcium ions. The aim of the present study was to establish whether the CPP effect on calcium uptake is specific for HT-29 cells and depends on the differentiated state of the cells. To this purpose, HT-29 and Caco2 cells, two models of intestinal cells, were differentiated following appropriate protocols, including treatment with 1,25-(OH)2 vitamin D3. The CPP-dependent intracellular calcium rises were monitored at the single-cell level through fura2-fluorescence assays, and cell differentiation was assessed by biochemical and morphological methods. Results clearly showed that the ability to take up extracellular calcium ions under CPP stimulation is exhibited by both HT-29 and Caco2 cells, but only upon cell differentiation. This evidence adds novel support to the notion that CPPs favour calcium absorption, thus possibly acting as cellular bio-modulators and carrying a nutraceutical potential.
aDepartment of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
bStrang Cancer Research Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA
cDMU, Department of Human Morphology, University of Milan, 20133 Milan, Italy
☆ This work was supported in part by the EU FAIR Programme Project CT98-3077 (“Caseinphosphopeptide (CPP): Nutraceutical/functional food ingredients for food and pharmaceutical applications”) and by Fondazione Romeo and Enrica Invernizzi (“CPP: role in the calcium intestinal absorption and its utilization. A perspective study on their possible usage as nutraceuticals or functional food to favour calcium bioavailability”).