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Pharmaceuticals 2017, 10(1), 5;

D11-Mediated Inhibition of Protein Kinase CK2 Impairs HIF-1α-Mediated Signaling in Human Glioblastoma Cells

Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark
Author to whom correspondence should be addressed.
Academic Editors: Joachim Jose, Marc Le Borgne, Lorenzo A. Pinna and Mathias Montenarh
Received: 1 November 2016 / Revised: 13 December 2016 / Accepted: 22 December 2016 / Published: 1 January 2017
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Compelling evidence indicates that protein kinase CK2 plays an important role in many steps of cancer initiation and progression, therefore, the development of effective and cell-permeable inhibitors targeting this kinase has become an important objective for the treatment of a variety of cancer types including glioblastoma. We have recently identified 1,3-dichloro-6-[(E)-((4-methoxyphenyl)imino)methyl]dibenzo(b,d)furan-2,7-diol (D11) as a potent and selective inhibitor of protein kinase CK2. In this study, we have further characterized this compound and demonstrated that it suppresses CK2 kinase activity by mixed type inhibition (KI 7.7 nM, KI′ 42 nM). Incubation of glioblastoma cells with D11 induces cell death and upon hypoxia the compound leads to HIF-1α destabilization. The analysis of differential mRNA expression related to human hypoxia signaling pathway revealed that D11-mediated inhibition of CK2 caused strong down-regulation of genes associated with the hypoxia response including ANGPTL4, CA9, IGFBP3, MMP9, SLC2A1 and VEGFA. Taken together, the results reported here support the notion that including D11 in future treatment regimens might turn out to be a promising strategy to target tumor hypoxia to overcome resistance to radio- and chemotherapy. View Full-Text
Keywords: CK2; D11; HIF-1α; glioblastoma cells; gene expression profiling CK2; D11; HIF-1α; glioblastoma cells; gene expression profiling

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Schaefer, S.; Svenstrup, T.H.; Fischer, M.; Guerra, B. D11-Mediated Inhibition of Protein Kinase CK2 Impairs HIF-1α-Mediated Signaling in Human Glioblastoma Cells. Pharmaceuticals 2017, 10, 5.

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