title: Comparative assessment of the cytotoxic effects of carboxylato-bridged dinuclear platinum (II) complexes against human tumor cell lines.
abstract: The cytotoxic effects of a series of carboxylato-bridged dinuclear platinum (II) complexes with acetate (BAP), propionate (BPP) and valerate (BVP) ligands were evaluated in a panel of human tumor cell lines. BAP proved to be the most potent antineoplastic agent, whose cytotoxic effect reached and even outclassed that of the referent drug cisplatin. This compound also exerted substantial efficacy against a broader spectrum of tumor models including the multidrug-resistant HL-60/Dox cell line. In the latter case, BAP showed lower resistance index than cisplatin. BAP was furthermore found to induce apoptosis in different cell lines as evidenced by DNA-laddering and Cell-death ELISA. Our experimental data give us reason to conclude that the dinuclear Pt(II) complex with acetate ligands is perspective for further detailed pharmacological and toxicological evaluation as an antineoplastic drug candidate.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University-Sofia, 1000, Sofia, Bulgaria.
authors.forename: G
authors.initials: G
authors.lastname: Momekov
authors.forename: A
authors.initials: A
authors.lastname: Bakalova
authors.forename: S
authors.initials: S
authors.lastname: Konstantinov
authors.forename: D
authors.initials: D
authors.lastname: Todorov
authors.forename: M
authors.initials: M
authors.lastname: Karaivanova
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D008024:Ligands; D009944:Organoplatinum Compounds