A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells
Copyright policy )A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells
Six novel compounds of platinum(II) with pyrazole derivatives PtPz1–PtPz6 were synthesised and characterised (PtPz1 - [Pt2N-hydroksymethyl-3,5-dimethylpyrazole4(berenil)2]Cl4; PtPz2 - [Pt23,5-dimethylpyrazole4(berenil)2]Cl4; PtPz3 - [Pt23,4-dimethylpyrazole4(berenil)2]Cl4; PtPz4 - [Pt2pyrazole4(berenil)2]Cl4; PtPz5- [Pt25-methylpyrazole4(berenil)2]Cl4; PtPz6 - [Pt2N-ethylpyrazole4(berenil)2]Cl4). The cytotoxic activity of these complexes against MCF-7 and MDA-MB-231 breast cancer cell lines was determined using the MTT assay. Evaluation of apoptosis induction was done with the Annexin V-fluorescein isothiocyanate/propidium iodide assay. In addition, using a flow cytometer, we determined the influence of test compounds on the cell cycle and caspase-3, -8, and -9 activity. The obtained results of caspase activity were confirmed by cell imaging. Moreover, using the flow cytometer, the effects of the test compounds on mitochondrial potential change were assessed. The test results showed that novel pyrazole-platinum(II) complexes exhibited stronger anti-proliferative activity against two breast cancer cell lines than reference cisplatin. Compounds PtPz1, PtPz2, and PtPz3 with methyl substituents at the pyrazole ring showed stronger activity than pyrazole or ethylpyrazole containing complexes. Studies have shown that inhibition of cell survival occurs by arresting the G1 cell cycle and inducing apoptosis. Our analysis associated with the response of MCF-7 and MDA-MB-231 cells to treatment with PtPz1–PtPz6 showed that it leads the cells through the external and intrinsic (mitochondrial) apoptotic pathway via indirect DNA damage.
- Wrocław Medical University Poland
- Medical University of Białystok Poland
Organoplatinum compounds - pharmacology, Dose-response relationship, Organoplatinum Compounds, Antineoplastic agents - pharmacology, Apoptosis, mitochondrial - drug effects, Anti-cancer drugs, Pyrazoles - pharmacology, Tumor Cells, Cultured, Cell survival - drug effects, Antineoplastic agents - chemical synthesis, MCF-7 cells, antitumor, Membrane Potential, Mitochondrial, Molecular Structure, apoptosis, drug, Organoplatinum compounds - chemistry, Breast neoplasms - drug therapy, Antineoplastic agents - chemistry, Drug screening assays, Caspases, MCF-7 Cells, Female, Research Paper, Cell Survival, Apoptosis - drug effects, Pyrazoles - chemistry, Antineoplastic Agents, Breast Neoplasms, RM1-950, Tumor cells, Organoplatinum compounds - chemical synthesis, Breast neoplasms - pathology, Structure-Activity Relationship, Breast neoplasms - metabolism, Humans, cultured, Membrane potential, Cell Proliferation, Caspases - metabolism, Dose-Response Relationship, Drug, Cell Cycle Checkpoints, Structure-activity relationship, pyrazole, Cell proliferation - drug effects, Pyrazoles, Cell cycle checkpoints - drug effects, Therapeutics. Pharmacology, Drug Screening Assays, Antitumor, Molecular structure, platinum complexes
Organoplatinum compounds - pharmacology, Dose-response relationship, Organoplatinum Compounds, Antineoplastic agents - pharmacology, Apoptosis, mitochondrial - drug effects, Anti-cancer drugs, Pyrazoles - pharmacology, Tumor Cells, Cultured, Cell survival - drug effects, Antineoplastic agents - chemical synthesis, MCF-7 cells, antitumor, Membrane Potential, Mitochondrial, Molecular Structure, apoptosis, drug, Organoplatinum compounds - chemistry, Breast neoplasms - drug therapy, Antineoplastic agents - chemistry, Drug screening assays, Caspases, MCF-7 Cells, Female, Research Paper, Cell Survival, Apoptosis - drug effects, Pyrazoles - chemistry, Antineoplastic Agents, Breast Neoplasms, RM1-950, Tumor cells, Organoplatinum compounds - chemical synthesis, Breast neoplasms - pathology, Structure-Activity Relationship, Breast neoplasms - metabolism, Humans, cultured, Membrane potential, Cell Proliferation, Caspases - metabolism, Dose-Response Relationship, Drug, Cell Cycle Checkpoints, Structure-activity relationship, pyrazole, Cell proliferation - drug effects, Pyrazoles, Cell cycle checkpoints - drug effects, Therapeutics. Pharmacology, Drug Screening Assays, Antitumor, Molecular structure, platinum complexes
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