Peptides From the N-terminal End of Bovine Lactoferrin Induce Apoptosis in Human Leukemic (HL-60) Cells

Abstract

To determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF) and related compounds on the growth of leukemic cells, human myeloid leukemic cells (HL-60) were exposed to bovine lactoferrin (bLF) and proteolytic hydrolysates of bLF. Pepsin hydrolysates of bLF showed a greater growth suppressive effect than tryptic hydrolysates or mature bLF. Four peptides with proliferation inhibition activity were purified from pepsin hydrolysates by ion-exchange chromatography, reverse-phase HPLC, and gel-filtration. All peptides were from the N-terminal end, in a region where lactoferricin B (Lfcin B), an antibacterial peptide, is located. Among the four peptides, peptide 1 (pep1) was found to exhibit highest activity and corresponded to residues 17 to 38 of bLF, with a molecular weight of 2753.88. The IC50 value of this peptide was 6.3 micrograms/ml. Three other peptides were less active and corresponded to sequences 1 to 16 and 45 to 48, linked by disulfide-bridge (pep2, molecular mass of 2430.13), 1 to 15 and 45 to 46 linked by disulfide bridge (pep3, molecular mass of 2017,92) and from residues 1 to 13 (pep4, molecular mass of 1558.73). Cell proliferation inhibition activity of the peptides was thought to be due to induction of apoptosis, which was evaluated by DNA ladder formation, DNA fragmentation, enhanced expression of phosphatidyl serine, and morphological changes. The IC50 values of the three peptides were confirmed using synthetic peptides and were consistent with those of purified peptides.

Propriedades fisiológicas-funcionais das proteínas do soro de leite

“…A lactoferricina, peptídio formado dos resíduos 17-41, resultante da ação da pepsina sobre a lactoferrina, apresenta além da atividade antimicrobiana 23 , ação apoptótica sobre células da leucemia humana 24 .…”

Peptides from water buffalo cheese whey induced senescence cell death via ceramide secretion in human colon adenocarcinoma cell line

“…The antioxidant activity of milk protein hydrolysates has been interestingly described [24][25][26][27], and also individual peptide released after hydrolysis from a s -casein have been shown to possess free radical scavenging activities inhibiting enzymatic and nonenzymatic lipid peroxidation [28]. Moreover, a number of recent studies have shown that milk-derived peptides exert cytomodulatory activity playing a role in the regulation of cell growth, differentiation, and apoptosis [29][30][31]. A previous study on the CaCo2 cell line suggested that the complex peptide fraction of the buffalo milk waste whey (BWW), resulting from production of buffalo Mozzarella cheese had antioxidant and cytomodulatory properties [32].…”

Conformational study of bovine lactoferricin in membrane-micking conditions by molecular dynamics simulation and circular dichroism

“…It was reported that bovine Lactoferricin (LfcinB) has antimicrobial activity higher than the intact protein bovine Lactoferrin (LfB) (Bellamy et al 1992a, b;Bellamy et al 1994), and that it is the most active among the other Lfcins of human, murine and caprine origin (Vorland et al 1998). Moreover, not only is LfcinB active against gram-positive as well as gram-negative bacteria, fungi, and protozoa Gifford et al 2005), but it also shows antiviral and antitumor properties (Anderson et al 2003;Eliassen et al 2002;Roy et al 2002).…”