Reduction of Ultraviolet Light-Induced DNA Damage in Human Colon Cancer Cells Treated With a Lactoferrin-Derived Peptide

J Dairy Sci. 2012 Oct;95(10):5552-60. doi: 10.3168/jds.2011-5279. Epub 2012 Aug 15.

Abstract

Treatment of Caco-2 cells with the peptide lactoferricin(4-14), results in reduction of the growth rate by prolongation of the S phase of the cell cycle. Lactoferricin(1-25) is formed in the gut by cleavage from lactoferrin and the bioactive amino acids are found within lactoferricin(4-14). 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 2.0 μM lactoferricin(4-14). Evaluation of DNA strand breaks using the comet assay showed that lactoferricin(4-14) 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. Lactoferricin(4-14) treatment resulted in an increased expression of flap endonuclease-1 pointing to increased DNA synthesis activity. Lactoferricin(4-14) 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, lactoferricin(4-14) treatment reduced the expression of cyclin E involved in the G(1)/S transition. Immunofluorescence microscopy showed that a lower γ-H2AX expression in lactoferricin(4-14)-treated cells, pointing to more efficient DNA repair. Thus, altogether our data show that lactoferricin(4-14) treatment has beneficial effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Caco-2 Cells / drug effects*
  • Cell Line, Tumor
  • Comet Assay / methods
  • DNA Damage / drug effects*
  • DNA Repair / drug effects
  • Humans
  • Lactoferrin / pharmacology*
  • Peptide Fragments / pharmacology*
  • S Phase / drug effects
  • Ultraviolet Rays / adverse effects

Substances

  • Antineoplastic Agents
  • Peptide Fragments
  • lactoferricin 4-14, human
  • lactoferricin B
  • Lactoferrin