Lactoferrin induces growth arrest and nuclear accumulation of Smad-2 in HeLa cells.

Abstract

Lactoferrin (Lf) is a multifunctional glycoprotein. Due to its anti-inflammatory and anti-cancer properties and the resulting therapeutical potential, lactoferrin is at present focus of a variety of research areas. The regulation of cell growth represents one of the prominent performances of lactoferrin. In this study we found lactoferrin to inhibit proliferation of the human epithelial cancer cell line HeLa. The extent of this growth inhibition was comparable to the one induced by the transforming-growth-factor-beta-1 (TGFbeta1). In contrast to other cell lines where lactoferrin stimulates growth, lactoferrin failed to activate the MAP kinases ERK1/2 or p38 in HeLa cells. However, by immunocytochemistry and cell fractionation experiments, we found that lactoferrin is capable of activating the TGFbeta/Smad-2 pathway. The nuclear accumulation of Smad-2 induced by Lf was comparable in magnitude to the one induced by TGFbeta1. We therefore conclude that the canonical TGFbeta1 pathway is a feasible route for lactoferrin to transduce its antiproliferative effect in HeLa cells, when MAPkinase activation is absent.

• Authors: Nina Zemann, Petra Klein, Ellen Wetzel, Felix Huettinger, Manfred Huettinger
• Journal: Biochimie (Biochimie) Vol. 92 Issue 7 Pg. 880-4 (Jul 2010) ISSN: 1638-6183 [Electronic] France
• PMID: 20347004 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Smad2 Protein
• Transforming Growth Factor beta1
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• Lactoferrin

Topics

• Animals
• Cattle
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Enzyme Activation (drug effects)
• HeLa Cells
• Humans
• Kinetics
• Lactoferrin (pharmacology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Protein Transport (drug effects)
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)