Effects of Lactoferrin and Its Peptides on Proliferation of Rat Intestinal Epithelial Cell Line, IEC-18, in the Presence of Epidermal Growth Factor

• Published in: Bioscience, biotechnology, and biochemistry Vol. 59; no. 10; pp. 1875 - 1881
• Main Authors: Hagiwara, Tomoyuki, Shinoda, Ichizo, Fukuwatari, Yasuo, Shimamura, Seiichi
• Format: Journal Article
• Language: English
• Published: Tokyo Taylor & Francis 1995; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Biotechnology; Cattle; Cell Division - drug effects; Cell Line; Cell physiology; DNA - biosynthesis; Epidermal Growth Factor - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Hydrolysis; Intestinal Mucosa - cytology; Lactoferrin - pharmacology; Molecular and cellular biology; Molecular Sequence Data; Pepsin A - metabolism; Peptide Fragments - pharmacology; Rats; Responses to growth factors, tumor promotors, other factors; Transferrin - pharmacology; Cell proliferation; Ferroprotein; Molecular cooperativity; Rat; Rodentia; Iron; Ileum; In vitro; Vertebrata; Lactoferrin; Cell line; Mammalia; Epidermal growth factor
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.59.1875

The cell growth-stimulating activity of lactoferrin (LF) in combination with epidermal growth factor (EGF) was evaluated by using a rat intestinal epithelial cell line, IEC-18. LF was found to be more effective than EGF for inducing an increase in cell numbers when cultured for over 6 days using a medium containing 0.2% fetal calf serum (FCS), although the 3 H-thymidine incorporation-stimulating activity of EGF was more potent than that of LF. A synergistic effect of LF and EGF was observed in both cell proliferation and DNA synthesis assays. The increase in cell numbers when stimulated with LF plus EGF corresponded to about 5 times that of the control. Iron was not required for manifestation of these effects of LF. On the other hand, iron-saturated transferrin (TF) had cell-growth-stimulating activity, but iron-free TF did not, either in the presence or absence of EGF. These results indicate that LF induces cell proliferation by a mechanism distinct from that of TF. A pepsin-generated hydrolysate of LF (LFH) had an activity similar to that of undigested LF, and a peptide with cell-growth-stimulating activity from bovine LFH was isolated by monitoring its effects in combination with EGF on DNA synthesis in IEC-18 cells. Sequence analysis indicated that the peptide has the structure Ala-Glu-Ile-Tyr-Gly-Thr-Lys-Glu-Ser-Pro-Gln-Thr-His-TyrTyr, corresponding to residues 79-93 of bovine LF.