title: The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells.
abstract: BACKGROUND
  Prognosis of adult patients suffering from acute lymphoblastic leukemia (ALL) is still unsatisfactory. Targeted therapy via inhibition of deregulated signaling pathways appears to be a promising therapeutic option for the treatment of ALL. Herein, we evaluated the influence of a novel arylindolylmaleimide (PDA-66), a potential GSK3β inhibitor, on several ALL cell lines.
  
  
  METHODS
  ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were exposed to different concentrations of PDA-66. Subsequently, proliferation, metabolic activity, apoptosis and necrosis, cell cycle distribution and protein expression of Wnt and PI3K/Akt signaling pathways were analyzed at different time points.
  
  
  RESULTS
  PDA-66 inhibited the proliferation of ALL cells significantly by reduction of metabolic activity. The 72 h IC50 values ranged between 0.41 to 1.28 μM PDA-66. Additionally, caspase activated induction of apoptosis could be detected in the analyzed cell lines. PDA-66 influenced the cell cycle distribution of ALL cell lines differently. While RS4;11 and MOLT4 cells were found to be arrested in G2 phase, SEM cells showed an increased cell cycle in G0/1 phase.
  
  
  CONCLUSIONS
  PDA-66 displays significant antileukemic activity in ALL cells and classifies as candidate for further evaluation as a potential drug in targeted therapy of ALL.
authors: Christin
authors: C
authors: Kretzschmar
authors: Catrin
authors: C
authors: Roolf
authors: Tina-Susann
authors: TS
authors: Langhammer
authors: Anett
authors: A
authors: Sekora
authors: Anahit
authors: A
authors: Pews-Davtyan
authors: Matthias
authors: M
authors: Beller
authors: Moritz J
authors: MJ
authors: Frech
authors: Christian
authors: C
authors: Eisenlöffel
authors: Arndt
authors: A
authors: Rolfs
authors: Department of Hematology/Oncology/Palliative Medicine, Division of Medicine, University of Rostock, Ernst-Heydemann-Str, 6, Rostock 18057, Germany. christian.junghanss@med.uni-rostock.de.
authors: Christian
authors: C
authors: Junghanss
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D008301:Maleimides / Q000494:pharmacology*; D009336:Necrosis; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D008301:Maleimides; C579844:PDA-66; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3