Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: involvement of reactive oxygen species

Biochem Biophys Res Commun. 1997 Aug 28;237(3):624-8. doi: 10.1006/bbrc.1997.7199.


We examined the activity of bovine lactoferricin (Lfcin-B), a peptide derived from a bovine milk protein lactoferrin (LF-B), to induce apoptosis in THP-1 human monocytic leukemic cells. Treatment with Lfcin-B at up to 50 micrograms/ml induced cell death in THP-1 cells in dose- and time-dependent manner, showing apparent morphological changes, hypodiploid forms of genomic DNA and apoptotic DNA fragmentation, whereas LF-B was inactive even at a high dose (500 micrograms/ml). The apoptosis-inducing effect of Lfcin-B increased with reduction of serum concentration, but was inhibited by addition of Zn2+, a inhibitor of Ca2+/Mg(2+)-dependent endonucleases in a dose-dependent manner. Furthermore, Lfcin-B-induced apoptosis in THP-1 cells was completely abolished by addition of antioxidants such as N-acetyl-L-cysteine (NAC) and glutathione (GSH), but not by various cytokines and mitogen which can activate monocytic cells. In addition, THP-1 cells treated with Lfcin-B, but not LF-B, showed high levels of intracellular reactive oxygen species (ROS) from the early period (20 min) of Lfcin-B treatment. And the production of ROS by Lfcin-B was dependent upon the dose of Lfcin-B added. These results suggested that Lfcin-B, a LF-B-derived peptide, but not LF-B itself, is able to induce apoptosis in THP-1 human monocytic tumor cells, and that its apoptosis-inducing activity is related to the pathway mediated by production of the intracellular ROS and activation of Ca2+/Mg(2+)-dependent endonucleases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Cattle
  • DNA Fragmentation
  • DNA, Neoplasm / drug effects
  • Diploidy
  • Female
  • Glutathione / pharmacology
  • Humans
  • Kinetics
  • Lactoferrin / analogs & derivatives*
  • Lactoferrin / isolation & purification
  • Lactoferrin / pharmacology
  • Leukemia, Monocytic, Acute
  • Milk / chemistry*
  • Reactive Oxygen Species / metabolism*
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • Reactive Oxygen Species
  • lactoferricin B
  • Lactoferrin
  • Glutathione
  • Acetylcysteine