Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7- tetrabromo- 1H‑benzimidazole in breast cancer cell lines

Authors and Affiliations :

Department of Biomedical Research, National Medicines Institute, Chełmska St. 30/34, 00-725, Warsaw, PolandMirosława KoronkiewiczInstitute of Chemistry, Warsaw University of Life Sciences, Nowoursynowska St. 159C, 02-787, Warsaw, PolandZygmunt Kazimierczuk & Andrzej Orzeszko


Contributions :

MK, AO contributed to the study conception. AO and ZK performed synthesis of compound. MK methodology. MK conducted the all experiments. MK interpretation of data. MK writing-original draft preparation and editing. AO, MK reviewed the article. All authors read and approved the final manuscript.


Abstract :

Background :

The protein kinases CK2 and PIM-1 are involved in cell proliferation and survival, the cell cycle, and drug resistance, and they are found overexpressed in virtually all types of human cancer, including breast cancer. In this study, we investigated the antitumor activity of a deoxynucleoside derivative, the protein kinase inhibitor compound 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (K164, also termed TDB), inter alia CK2 and PIM-1, on breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3).

Methods :

An evaluation of the cytotoxic and proapoptotic effects, mitochondrial membrane potential (ΔΨm), and cell cycle progression was performed using an MTT assay, flow cytometry, and microscopic analysis. The Western blotting method was used to analyze the level of proteins important for the survival of breast cancer cells and proteins phosphorylated by the CK2 and PIM-1 kinases.

Results :

The examined compound demonstrated the inhibition of cell viability in all the tested cell lines and apoptotic activity, especially in the MCF-7 and SK-BR-3 cells. Changes in the mitochondrial membrane potential (ΔΨm), cell cycle progression, and the level of the proteins studied were also observed.


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