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

• Published in: Macromolecular bioscience 2017-05, Vol.17 (5), p.n/a
• Main Authors: Franiak‐Pietryga, Ida, Ostrowska, Kinga, Maciejewski, Henryk, Appelhans, Dietmar, Misiewicz, Małgorzata, Ziemba, Barbara, Bednarek, Michał, Bryszewska, Maria, Borowiec, Maciej
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Cancer; Cell Line, Tumor; Chemotherapy; Chronic lymphocytic leukemia; chronic lymphocytic leukemia (CLL); Color; Dendrimers - chemistry; Dendrimers - pharmacology; DNA microarrays; Fludarabine; Gene expression; Gene Expression - drug effects; glycodendrimers; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphatic leukemia; Maltotriose; Oligonucleotide Array Sequence Analysis; Polypropyleneimine; Polypropylenes - pharmacology; Propylene imine; Signal Transduction; signaling pathway; Therapy; TNF; TNF-Related Apoptosis-Inducing Ligand - physiology; TRAIL protein; Tumor necrosis factor; Tumor necrosis factor-TNF; Up-Regulation - drug effects; Vidarabine - analogs & derivatives; Vidarabine - pharmacology
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201600169

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. The study shows the proapoptotic effects of poly(propylene imine) (PPI) dendrimers with maltotriose (PPI‐G4‐OS/DS‐Mal‐III) on the tumor necrosis factor‐related apoptosis‐inducing ligand in chronic lymphocytic leukemia cells. The development of a molecular profiling is a key issue for the design of personalized approaches to cancer therapy.