Comparison of Bioactivities of Talactoferrin and Lactoferrins From Human and Bovine Milk

Objectives: Lactoferrin (Lf) is an iron-binding glycoprotein present in high concentration in human milk. It is a pleiotropic protein and is involved in diverse bioactivities, such as stimulation of cell proliferation and differentiation, immune competence, antimicrobial activities, anti-infection, and anticancer activities. Lf has been shown to be partly resistant to proteolysis in the gastrointestinal tract and may thus play important roles in the intestine and liver during infancy. Talactoferrin alfa (TLf) is a recombinant human Lf shown to protect against sepsis and necrotizing enterocolitis as well as cancer. Because bovine Lf (bLf) and human Lf have different amino acid composition and all 3 Lfs differ in glycosylation, they may have different functions/potency. The objective of the present study was to investigate and compare bioactivities of TLf and Lfs from human and bovine milk and thus to provide a better understanding of the bioactivities of different forms of Lf and their potential applications. Methods: In the present study, Caco-2 and C3A cells were used as intestine and liver models to evaluate internalization of Lfs by intestine and liver cells, effects of Lfs on cell proliferation and differentiation, growth of enteropathogenic Escherichia coli (EPEC), chemokine (C-C motif) ligand 20 (CCL20) secretion, and transforming growth factor (TGF)-beta 1 expression. In addition, HT-29 cells were used as a colon cancer cell model to examine the effects of Lfs on apoptosis. Results: All Lfs significantly enhanced cell proliferation and differentiation, apoptosis, CCL20 secretion, and TGF-beta 1 expression. They also markedly suppressed growth of EPEC. Compared with bLf, TLf showed stronger effects on suppression of EPEC growth and enhancement of TGF-beta 1 secretion, whereas bLf exhibited more potent effects on cell differentiation, apoptosis, and CCL20 secretion. Conclusions: Our results demonstrate that TLf has several bioactivities similar to human Lf and bLf from milk and may play critical roles in immune and intestinal development in infants as well as having anti-cancer activities in adults. TLf and bLf may be used for different applications owing to their various potencies. TLf may preferentially be used for anti-bacterial applications, whereas bLf may be used for cancer therapy because it exhibits stronger effects on CCL20 secretion, cell differentiation, and apoptosis.