The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells

作者：Kretzschmar Christin; Roolf Catrin; Langhammer Tina Susann; Sekora Anett; Pews Davtyan Anahit; Beller Matthias; Frech Moritz J; Eisenloeffel Christian; Rolfs Arndt; Junghanss Christian^*

来源：BMC Cancer, 2014, 14(1): 71.

DOI：10.1186/1471-2407-14-71

• Arylindolylmaleimide
• Glycogen Synthase Kinase 3 beta
• Acute lymphoblastic leukemia
• Apoptosis
• Enzyme inhibitors

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 GSK3 beta inhibitor, on several ALL cell lines. %26lt;br%26gt;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. %26lt;br%26gt;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 mu M 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. %26lt;br%26gt;Conclusion: 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.

• 出版日期2014-2-6