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Reduction of ultraviolet light-induced DNA damage in human colon cancer cells treated with a lactoferrin-derived peptide

Freiburghaus, Catja LU ; Lindmark-Mansson, H.; Paulsson, Marie LU and Oredsson, Stina LU (2012) In Journal of Dairy Science 95(10). p.5552-5560
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 mu M 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... (More)
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 mu M 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 gamma-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DNA strand break, DNA repair, comet assay, lactoferricin(4-14)
in
Journal of Dairy Science
volume
95
issue
10
pages
5552 - 5560
publisher
American Dairy Science Association
external identifiers
  • wos:000309084600009
  • pmid:22901475
  • scopus:84867101768
ISSN
1525-3198
DOI
10.3168/jds.2011-5279
language
English
LU publication?
yes
id
d345a297-5c10-4dc7-a6c9-14382e5034e6 (old id 3190022)
date added to LUP
2012-12-04 08:29:40
date last changed
2017-01-01 03:16:30
@article{d345a297-5c10-4dc7-a6c9-14382e5034e6,
  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 mu M 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 gamma-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.},
  author       = {Freiburghaus, Catja and Lindmark-Mansson, H. and Paulsson, Marie and Oredsson, Stina},
  issn         = {1525-3198},
  keyword      = {DNA strand break,DNA repair,comet assay,lactoferricin(4-14)},
  language     = {eng},
  number       = {10},
  pages        = {5552--5560},
  publisher    = {American Dairy Science Association},
  series       = {Journal of Dairy Science},
  title        = {Reduction of ultraviolet light-induced DNA damage in human colon cancer cells treated with a lactoferrin-derived peptide},
  url          = {http://dx.doi.org/10.3168/jds.2011-5279},
  volume       = {95},
  year         = {2012},
}