TY - JOUR T1 - Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL. JF - Invest New Drugs Y1 - 2012 A1 - Gonelli, Arianna A1 - Radillo, Oriano A1 - Drioli, Sara A1 - Rimondi, Erika A1 - Secchiero, Paola A1 - Maria Bonora, Gian KW - Antineoplastic Agents KW - Apoptosis KW - Caspase 3 KW - Cell Movement KW - Dose-Response Relationship, Drug KW - HL-60 Cells KW - Humans KW - Leukemia KW - Mesenchymal Stromal Cells KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinase 3 KW - Phosphorylation KW - Polyethylene Glycols KW - Recombinant Fusion Proteins KW - Signal Transduction KW - Time Factors KW - TNF-Related Apoptosis-Inducing Ligand AB -

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.

VL - 30 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21125311?dopt=Abstract ER -