Inhibition of CK1 affects Viability and Survival of Glioblastoma Cells

Joachim Bischof¹*, Anna-Laura Kretz¹,Timo Burster², Doris Henne-Bruns¹, Uwe Knippschild¹ and Pengfei Xu¹

Received: January 24, 2018;   Published: February 06, 2018

DOI: 10.26717/BJSTR.2018.02.000735

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Abstract

Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor with an inevitable fatal outcome. However, the complex network of dysregulated pathways in glioblastoma development and progression remains to be poorly understood. Consequently, novel approaches for the treatment of glioblastoma are seriously needed and the search for new target molecules for pharmacologic intervention is in the focus of research. Since it is known that CK1 isoforms are involved in Wnt/β-catenin and sonic hedgehog signal transduction pathways, which are often dysregulated in glioblastoma cells, inhibition of CK1 isoforms might hold therapeutic potential. Therefore, two previously characterized CK1 isoform-selective difluoro-dioxolo-benzoimidazole derivatives were investigated on their effects on the viability of glioblastoma cell lines. Compound 2 showed major effects on the tested cells with EC₅₀ values below 100 nM in most of the analyzed glioblastoma cell lines. Cell cycle analyses underlined the observation that compound 2 is most effective since treatment with compound 2 induced cell death in up to 57% of the analyzed cells. In conclusion, our data point to a high therapeutic potential of CK1 isoform-selective inhibitors for the treatment of glioblastoma.

Keywords: CK1: Casein Kinase 1; GBM: Glioblastoma; Small Molecule Inhibitor, Kinase Inihbitor, MTT Assay, Flow Cytometry, Cell Cycle

Abbreviations: CK1: Casein Kinase 1; DMSO: Dimethylsulfoxide; EC₅₀: Half Maximal Effective Concentration; GBM: Glioblastoma Multiforme; MTT, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide; SHH: Sonic Hedgehog

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