Casein kinase II (CK2) is the most pleiotropic of all protein kinases with more than 300 substrates implicated in a wide variety of cellular functions as signal transduction, proliferation and cell survival. Increased levels of CK2 has been demonstrated in a number of cancers where regulates the activity of various oncoproteins and tumor suppressor proteins.  Therefore, CK2 inhibitors could be considered as potential anticancer drugs in monotherapy or in combination with known cytostatics. In this study we used a new strong CK2 inhibitor -4,5,6,7-tetraiodobenzimidazole (TIBI) (IC50 = 38 nM) as well as its 2-substituted derivatives. TIBI was obtained by iodination of benzimidazole with iodine in sulfuric acid-periodic acid mixture. The substitution of 2-bromo-4,5,6,7-tetraiodobenzimidazole with piperidine, piperazine (TIBIPIP) and N-methylpiperazine provided the respective 2-modified 4,5,6,7-tetraiodobenzimidazoles (TBIPIP). The CK2 inhibitor (TIBI) and its two derivatives (TIBIPIP, TBIPIP) were tested for determination of the proapoptotic and cytostatic effects on the promyelocytic leukemia cell line (HL-60). The flow-cytometry results of the tested compounds showed that apoptotic effect was concentration and time dependent. The changes of the mitochondrial membrane potential and cell cycle progression were also observed.

The study was supported by the Foundation for Development Diagnostics and Therapy, Warsaw, Poland (AO i ZK).

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