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Open Access Research article

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

Christin Kretzschmar1, Catrin Roolf1, Tina-Susann Langhammer1, Anett Sekora1, Anahit Pews-Davtyan2, Matthias Beller2, Moritz J Frech3, Christian Eisenlöffel3, Arndt Rolfs34 and Christian Junghanss1*

Author Affiliations

1 Department of Hematology/Oncology/Palliative Medicine, Division of Medicine, University of Rostock, Ernst-Heydemann-Str. 6, Rostock 18057, Germany

2 Leibniz-Institute for Catalysis at the University of Rostock, Albert-Einstein-Str. 29a, Rostock 18059, Germany

3 Albrecht-Kossel-Institute for Neuroregeneration (Akos), Center for Mental Health, University of Rostock, Gehlsheimerstr. 20, Rostock 18147, Germany

4 Centogene AG, Schillingallee 68, Rostock 18057, Germany

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BMC Cancer 2014, 14:71  doi:10.1186/1471-2407-14-71

Published: 6 February 2014

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.

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.

Keywords:
Arylindolylmaleimide; Glycogen Synthase Kinase 3β; Acute lymphoblastic leukemia; Apoptosis; Enzyme inhibitors