Biological evaluation of dimethylpyridine–platinum complexes with potent antiproliferative activity. (3rd November 2016)

• Record Type: Journal Article
• Authors: Czarnomysy, Robert; Bielawski, Krzysztof; Muszynska, Anna; Bielawska, Anna; Gornowicz, Agnieszka
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31(2016:Jun.)Supplement 3
• Page Start: 150
• Page End: 165
• Publication Date: 2016-11-03
• Subjects: Apoptosis -- anticancer drugs -- cytotoxicity -- platinum complexes -- flow cytometry; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2016.1212191
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: 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.