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

BMC Cancer

Christian Junghanss²  Arndt Rolfs¹  Christian Eisenlöffel⁴  Moritz J Frech⁴  Matthias Beller³  Anahit Pews-Davtyan³  Anett Sekora²  Tina-Susann Langhammer²  Catrin Roolf²  Christin Kretzschmar² 

[1]Centogene AG, Schillingallee 68, Rostock 18057, Germany

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

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

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

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

Others  :  859086
DOI  :  10.1186/1471-2407-14-71

 received in 2013-08-16, accepted in 2014-02-02,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Kretzschmar et al.; licensee BioMed Central Ltd.

【 图 表 】

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