Department of Biomedical Research, National Medicines Institute, Chełmska St. 30/34, 00-725, Warsaw, Poland.
Institute of Chemistry, Warsaw University of Life Sciences, Nowoursynowska St. 159C, 02-787, Warsaw, Poland.
BMC Cancer. 2022 Oct 15;22(1):1069. doi: 10.1186/s12885-022-10156-8.
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).
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.
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.
The investigated CK2 and PIM-1 kinase inhibitor K164 is a promising compound that can be considered a potential agent in targeted therapy in selected types of breast cancer; therefore, further research is necessary.
蛋白激酶 CK2 和 PIM-1 参与细胞增殖和存活、细胞周期以及耐药性，几乎在所有类型的人类癌症中都过度表达，包括乳腺癌。在这项研究中，我们研究了脱氧核苷衍生物、蛋白激酶抑制剂化合物 1-（β-D-2'-脱氧呋喃核糖基）-4,5,6,7-四溴-1H-苯并咪唑（K164，也称为 TDB）对乳腺癌细胞系（MDA-MB-231、MCF-7 和 SK-BR-3）的抗肿瘤活性。
使用 MTT 测定法、流式细胞术和显微镜分析评估细胞毒性和促凋亡作用、线粒体膜电位（ΔΨm）和细胞周期进程。使用 Western blot 分析方法来分析对乳腺癌细胞存活很重要的蛋白质以及 CK2 和 PIM-1 激酶磷酸化的蛋白质的水平。
在所测试的所有细胞系中，该化合物均表现出抑制细胞活力和促凋亡活性，尤其是在 MCF-7 和 SK-BR-3 细胞中。还观察到线粒体膜电位（ΔΨm）、细胞周期进程以及研究中蛋白质水平的变化。
研究的 CK2 和 PIM-1 激酶抑制剂 K164 是一种很有前途的化合物，可被认为是选定类型的乳腺癌中靶向治疗的潜在药物；因此，有必要进行进一步的研究。
