Freiburghaus C, Lindmark-MAnsson H, Paulsson M, Oredsson S. - 43124 N - J Dairy Sci 2012 ; 95(10) : 5552-5560.
Treatment of Caco-2 cells with the peptide lactoferricin4-14, results in reduction of the growth rate by prolongation of the S phase of the cell cycle. Lactoferricin1-25 is formed in the gut by cleavage from lactoferrin and the bioactive amino acids are found within lactoferricin4-14. Our hypothesis is that the reduction of the rate of S phase progression may result in increased DNA repair. To test this hypothesis, Caco-2 cells were subjected to UV light that caused DNA lesions and then the cells were grown in the absence or presence of 2.0µM lactoferricin4-14. Evaluation of DNA strand breaks using the comet assay showed that lactoferricin4-14 treatment indeed resulted in a reduction of comets showing damaged DNA. In the search for a mechanism, we have investigated the levels of several proteins involved in cell cycle regulation, DNA replication, and apoptosis using Western blot. Lactoferricin4-14 treatment resulted in an increased expression of flap endonuclease-1 pointing to increased DNA synthesis activity. Lactoferricin4-14 treatment decreased the expression of the proapoptotic protein B-cell lymphoma 2-associated X protein (or Bax), indicating decreased cell death. As we have found previously, lactoferricin4-14 treatment reduced the expression of cyclin E involved in the G1/S transition. Immunofluorescence microscopy showed that a lower gamma-H2AX expression in lactoferricin4-14-treated cells, pointing to more efficient DNA repair. Thus, altogether our data show that lactoferricin4-14 treatment has beneficial effects.