Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL

Invest New Drugs. 2012 Apr;30(2):828-32. doi: 10.1007/s10637-010-9599-8. Epub 2010 Dec 2.

Abstract

To improve the pharmacokinetic profile of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) an N-terminal specific pegylation was performed to generate pegylated TRAIL (PEG-TRAIL). In in vitro experiments, we found that although PEG-TRAIL was slightly less efficient than recombinant TRAIL in promoting leukemic cell apoptosis, it showed an improved ability to promote migration of bone-marrow mesenchymal stem cells and to elicit the ERK1/2 intracellular signal transduction pathway. Overall, these data suggest that TRAIL pegylation retains, or even enhances, the biological activities of TRAIL relevant for its therapeutic applications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • HL-60 Cells
  • Humans
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Polyethylene Glycols / pharmacology*
  • Recombinant Fusion Proteins / pharmacology*
  • Signal Transduction / drug effects*
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • PEGylated tumor necrosis factor-related apoptosis-inducing ligand
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Polyethylene Glycols
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • CASP3 protein, human
  • Caspase 3