title: Synthesis and proapoptotic properties of new casein kinase II inhibitors.
abstract: 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 it 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 examined proapoptotic activity of new strong CK2 inhibitor - 4,5,6,7-tetraiodobenzimidazole (TIBI) (IC50 = 38 nM) as well as new derivatives of 4,5,6,7-tetrabromobenzimidazole and 4,5,6,7-tetraiodobenzimidazole. All the tested compounds induced apoptosis and cytostatic effects in the promyelocytic leukemia cell line (HL-60). The proapoptotic effect was concentration and time dependent. The changes of the mitochondrial membrane potential and cell cycle progression were also observed.
authors.affiliation: National Medicines Institute, 30/34 Chełmska St., 00-750 Warszawa, Poland.
authors.forename: Mirosława
authors.initials: M
authors.lastname: Koronkiewicz
authors.forename: Magda
authors.initials: M
authors.lastname: Zukowska
authors.forename: Zdzisław
authors.initials: Z
authors.lastname: Chilmonczyk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Orzeszko
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Kazimierczuk
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II