Published December 20, 2016 | Version v1
Journal article Open

PPI‐G4 Glycodendrimers Upregulate TRAIL‐Induced Apoptosis in Chronic Lymphocytic Leukemia Cells

  • 1. Department of Clinical and Laboratory Genetics Medical University of Lodz 251 Pomorska Str., 92-213 Lodz, Poland; Laboratory of Clinical and Transplant Immunology and Genetics Copernicus Memorial Hospital 2 Pabianicka Str., 90-513 Lodz, Poland
  • 2. Laboratory of Clinical and Transplant Immunology and Genetics Copernicus Memorial Hospital 2 Pabianicka Str., 90-513 Lodz, Poland; Department of Immunobiology of Bacteria University of Lodz 12/16 Banacha Str., 90-231 Lodz, Poland
  • 3. Department of Computer Engineering Wroclaw University of Technology 5 Łukasiewicza Str., 50-371 Wroclaw, Poland
  • 4. Leibniz Institute of Polymer Research Dresden Hohe Straße 6, 01069 Dresden, Germany
  • 5. Department of Hematology Medical University of Lodz 251 Pomorska Str., 92-213 Lodz, Poland
  • 6. Department of General Biophysics Faculty of Biology and Environmental Protection University of Lodz 141/143 Pomorska Str., 90-236 Lodz, Poland
  • 7. Genos, 9 Inowrocławska Str., 91-020 Lodz, Poland
  • 8. Department of Clinical and Laboratory Genetics Medical University of Lodz 251 Pomorska Str., 92-213 Lodz, Poland

Description

Abstract

Although chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western world, it remains incurable with conventional chemotherapeutic agents. Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) is an antitumor candidate in cancer therapy. This study examines the proapoptotic effects of poly(propylene imine) (PPI) glycodendrimers modified with the maltotriose residues (PPI‐G4‐OS‐Mal‐III and PPI‐G4‐DS‐Mal‐III) on the TNF family in CLL cells. The combination of an understanding of the signaling pathways associated with CLL and the development of a molecular profiling is a key issue for the design of personalized approaches to therapy. Gene expression is determined with two‐color microarray 8 × 60K. The findings indicate that PPI‐G4‐OS/DS‐Mal‐III affect gene expression from the TRAIL apoptotic pathway and exert a strong effect on CLL cells comparable with fludarabine. Dendrimer‐targeted technology may well prove to bridge the gap between the ineffective treatment of today and the effective personalized therapy of the future.

Files

PPI-G4 Glycodendrimers Upregulate TRAIL-Induced Apoptosis in Chronic Lymphocytic Leukemia Cells.pdf