Journal
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume 31, Issue -, Pages 150-165Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2016.1212191
Keywords
Apoptosis; anticancer drugs; cytotoxicity; platinum complexes; flow cytometry
Funding
- Medical University of Bialystok [N/ST/ZB/15/002/2217]
- Medical University of Bialystok as part of the OP DEP [POPW.01.03.00-20-022/09]
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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.
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