Biological evaluation of dimethylpyridine–platinum complexes with potent antiproliferative activity
Copyright policy )Biological evaluation of dimethylpyridine–platinum complexes with potent antiproliferative activity
This study investigates the effect of three new platinum complexes: Pt2(2,4-dimethylpyridine)4(berenil)2 (Pt14), Pt2(3,4-dimethylpyridine)4(berenil)2 (Pt15) and Pt2(3,5-dimethylpyridine)4(berenil)2 (Pt16) on growth and viability of breast cancer cells and their putative mechanism(s) of cytotoxicity. Cytotoxicity was measured with MTT assay and inhibition of [3H]thymidine incorporation into DNA in both breast cancer cells. Results revealed that Pt14-Pt16 exhibit substantially greater cytotoxicity than cisplatin against MCF-7 and MDA-MB-231 breast cancer cells. In the case of human skin fibroblast cell, cytotoxicity assays demonstrated that these compounds are less toxic to normal cells than cisplatin. In addition, the effects of Pt14-Pt16 are investigated using the flow cytometry assessment of annexin V binding, analysis of mitochondrial potential, markers of apoptosis such as caspase-3, caspase-8, caspase-9, caspase-10 and defragmentation of DNA by TUNEL assay. These results indicate that Pt14-Pt16 induce apoptosis by the mitochondrial and external pathway.
- Wrocław Medical University Poland
- Medical University of Białystok Poland
Dose-response relationship, Organoplatinum Compounds, Cell Survival, Pyridines, Pyridines - pharmacology, Antineoplastic agents - pharmacology, Antineoplastic Agents, Platinum - chemistry, Tumor cells, Organoplatinum compounds - chemical synthesis, Structure-Activity Relationship, Tumor Cells, Cultured, Cell survival - drug effects, Humans, Antineoplastic agents - chemical synthesis, Flow cytometry, cultured, antitumor, Cell Proliferation, Platinum, Caspases - metabolism, Platinum - pharmacology, Dose-Response Relationship, Drug, Molecular Structure, drug, Organoplatinum compounds - chemistry, Pyridines - chemistry, Structure-activity relationship, Flow Cytometry, Antineoplastic agents - chemistry, Cell proliferation - drug effects, Drug screening assays, Caspases, Mitochondrial Membranes, Mitochondrial membranes - drug effects, Drug Screening Assays, Antitumor, Molecular structure
Dose-response relationship, Organoplatinum Compounds, Cell Survival, Pyridines, Pyridines - pharmacology, Antineoplastic agents - pharmacology, Antineoplastic Agents, Platinum - chemistry, Tumor cells, Organoplatinum compounds - chemical synthesis, Structure-Activity Relationship, Tumor Cells, Cultured, Cell survival - drug effects, Humans, Antineoplastic agents - chemical synthesis, Flow cytometry, cultured, antitumor, Cell Proliferation, Platinum, Caspases - metabolism, Platinum - pharmacology, Dose-Response Relationship, Drug, Molecular Structure, drug, Organoplatinum compounds - chemistry, Pyridines - chemistry, Structure-activity relationship, Flow Cytometry, Antineoplastic agents - chemistry, Cell proliferation - drug effects, Drug screening assays, Caspases, Mitochondrial Membranes, Mitochondrial membranes - drug effects, Drug Screening Assays, Antitumor, Molecular structure
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