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Open Access 01-12-2014 | Research article

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

Authors: Christin Kretzschmar, Catrin Roolf, Tina-Susann Langhammer, Anett Sekora, Anahit Pews-Davtyan, Matthias Beller, Moritz J Frech, Christian Eisenlöffel, Arndt Rolfs, Christian Junghanss

Published in: BMC Cancer | Issue 1/2014

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/71/prepub

Title: The novel arylindolylmaleimide PDA-66 displays pronounced antiproliferative effects in acute lymphoblastic leukemia cells
Authors: Christin Kretzschmar
Catrin Roolf
Tina-Susann Langhammer
Anett Sekora
Anahit Pews-Davtyan
Matthias Beller
Moritz J Frech
Christian Eisenlöffel
Arndt Rolfs
Christian Junghanss
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-14-71

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