Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines
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 deo...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10156-8 |
| _version_ | 1817983962751959040 |
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| author | Mirosława Koronkiewicz Zygmunt Kazimierczuk Andrzej Orzeszko |
| author_facet | Mirosława Koronkiewicz Zygmunt Kazimierczuk Andrzej Orzeszko |
| author_sort | Mirosława Koronkiewicz |
| collection | DOAJ |
| description | 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. Conclusions 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. |
| first_indexed | 2024-04-13T23:39:43Z |
| format | Article |
| id | doaj.art-526323faf7ee43288639c97874d1193c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T23:39:43Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-526323faf7ee43288639c97874d1193c2022-12-22T02:24:35ZengBMCBMC Cancer1471-24072022-10-0122111210.1186/s12885-022-10156-8Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell linesMirosława Koronkiewicz0Zygmunt Kazimierczuk1Andrzej Orzeszko2Department of Biomedical Research, National Medicines InstituteInstitute of Chemistry, Warsaw University of Life SciencesInstitute of Chemistry, Warsaw University of Life SciencesAbstract 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. Conclusions 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.https://doi.org/10.1186/s12885-022-10156-81-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazoleBreast cancer cell linesProtein kinase inhibitorApoptosisFlow cytometry |
| spellingShingle | Mirosława Koronkiewicz Zygmunt Kazimierczuk Andrzej Orzeszko Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines BMC Cancer 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole Breast cancer cell lines Protein kinase inhibitor Apoptosis Flow cytometry |
| title | Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines |
| title_full | Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines |
| title_fullStr | Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines |
| title_full_unstemmed | Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines |
| title_short | Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines |
| title_sort | antitumor activity of the protein kinase inhibitor 1 β d 2 deoxyribofuranosyl 4 5 6 7 tetrabromo 1h benzimidazole in breast cancer cell lines |
| topic | 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole Breast cancer cell lines Protein kinase inhibitor Apoptosis Flow cytometry |
| url | https://doi.org/10.1186/s12885-022-10156-8 |
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