A Cell Culture Model to Identify Biologically Active Peptides Generated by Bacterial Hydrolysis of Casein

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Abstract
Consumption of fermented dairy foods has been linked to reduced incidence of colon cancer in population groups. Recently, biologically active compounds have been isolated from these products. Bacterial proteinases, produced by dairy starter cultures, generate a variety of peptides from casein. Some of these casein-derived peptides are likely to alter intestinal cell kinetics. Effects on colon cell kinetics because of the presence of casein-derived peptides may be a mechanism through which fermented dairy foods reduce the risk of colon cancer. We have used two intestinal cell lines (IEC-6 cells, derived from normal rat intestine, and Caco-2 cells, derived from human colon adenocarcinoma) to identify casein peptides that affect intestinal cell kinetics. Cell culture media containing casein were inoculated with three commercial starter cultures and incubated for 4, 8, or 24 h. The bacteria-conditioned media were then filter-sterilized and incubated with the intestinal cells for 6 or 24 h. Rates of [3H]thymidine incorporation and cell cycle kinetics determined by flow cytometry were affected by the culture-modified media in both cell lines. The IEC-6 cells tended to reduce, and Caco-2 cells to increase, rates of cell division after exposure to the media. Intestinal cell response varied among the starter cultures. The results support the use of intestinal cell cultures to identify casein peptides generated by dairy starter cultures, which affect intestinal cell kinetics.