Effect of Simultaneous Inhibition of Protein Kinase CK2 and Thymidylate Synthase in Leukemia and Breast Cancer Cells
Autor: | Patrycja Wińska, Katarzyna Skierka, Joanna Cieśla, Edyta Łukowska-Chojnacka, Maria Bretner, Mirosława Koronkiewicz |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research Combination therapy Antineoplastic Agents Apoptosis Breast Neoplasms Thymidylate synthase Flow cytometry 03 medical and health sciences Western blot Cell Line Tumor medicine Humans MTT assay Naphthyridines Casein Kinase II Protein Kinase Inhibitors Leukemia medicine.diagnostic_test biology Chemistry Thymidylate Synthase General Medicine medicine.disease 030104 developmental biology Oncology Cell culture MCF-7 Cells Cancer research biology.protein Phenazines Benzimidazoles Female Fluorouracil |
Zdroj: | Anticancer Research. 38:4617-4627 |
ISSN: | 1791-7530 0250-7005 |
Popis: | Background/aim Protein kinase CK2 was recently identified as a promising therapeutic target for combination therapy. Our study aims to investigate the anticancer effect of a simultaneous inhibition of thymidylate synthase (TS) and CK2 in MCF-7 breast cancer and CCRF-CEM leukemia cells. Materials and methods The type of interaction between CK2 inhibitors: CX-4945, 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi), or recently obtained 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazol-1-yl)acetonitrile (2b) and TS-directed anticancer drug, 5-fluorouracil (5-FU) was determined using the MTT assay and a combination index method. The influence of the combined treatment on apoptosis in leukemia cells, as well as on cell-cycle progression and the levels of TS, CK2α and P-Ser529-p65 were determined in both cell lines, using flow cytometry and western blot analysis, respectively. Results The best synergistic effect was observed in CCRF-CEM cell line with the combination of 5-FU and 2b which correlated with a decrease in the endocellular CK2 activity and enhancement of the pro-apoptotic effect. Conclusion The obtained results demonstrate the ability of CK2 inhibitors to enhance the efficacy of 5-FU in anticancer treatment, indicating a different molecular mechanism of the studied CK2 inhibitors interaction with 5-FU. |
Databáze: | OpenAIRE |
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