title: Biological evaluation of dimethylpyridine-platinum complexes with potent antiproliferative activity.
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.
authors.affiliation: a Department of Synthesis and Technology of Drugs and.
authors.forename: Robert
authors.initials: R
authors.lastname: Czarnomysy
authors.affiliation: a Department of Synthesis and Technology of Drugs and.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bielawski
authors.affiliation: a Department of Synthesis and Technology of Drugs and.
authors.forename: Anna
authors.initials: A
authors.lastname: Muszynska
authors.affiliation: b Department of Biotechnology , Medical University of Bialystok , Bialystok , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielawska
authors.affiliation: b Department of Biotechnology , Medical University of Bialystok , Bialystok , Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gornowicz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D051336:Mitochondrial Membranes / Q000187:drug effects; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; D010984:Platinum; C521455:3,5-dimethylpyridine; D020169:Caspases
keywords: Apoptosis; anticancer drugs; cytotoxicity; flow cytometry; platinum complexes