Combining Temozolomide with a Selective CK2 Inhibitor Results in Anti-Tumour Effects in Glioblastoma Cell Lines

Abstract

Glioblastoma is one of the most aggressive tumours with a poor prognosis and a modest survival rate after diagnosis. Several trials for a more targeted and effective treatment are in progress. Protein kinase CK2 is upregulated in glioblastoma and creates a favourable environment for cell proliferation by supporting several survival pathways. Inhibitors of CK2 kinase activity were shown to restrict growth rate or to induce apoptosis in dif ferent cell culture and animal models. Recently, we described the selective CK2 inhibitor 6,7-dichloro-1,4-dihydro-8-hydroxy-4(4 methylphenylamino)methylen]dibenzo [b,d]furan 3(2H)-one (TF). In this study, we found that TF effectively reduces the proliferation of A1207 glioblastoma cells with an EC50 value of 13.7 µM, which is equal to the EC50 value of CX-4945, which was the first CK2 inhibitor in clinical phase II trials (13.9 µM). We investigated the effect of TF and temozolomide (TMZ) as a single or combination treatment in two glioblastoma cell lines, A1207 and U87. The treatment was carried out over 48 or 72 h, and, subsequently, the biological effects were evaluated. The proliferation of both cell lines was significantly impaired by the application of the drugs, and combination treatment with TF and TMZ proved superior to the individual treatments. Not only proliferation, as determined by cell confluence assays and BrdU incorporation, but also viability in terms of metabolic activity and cytotoxicity were affected by the treatment. The decrease in proliferation and viability is partly due to the induction of apoptosis, with both cell lines differing in terms of the pattern of apoptotic caspases. Taken together, TF in combination with TMZ may be a promising candidate for the treatment of glioblastoma in the future.