title: Study of antitumor effect of selected vanadium and molybdenum organometallic complexes in human leukemic T-cells.
abstract: This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(η(5)-C5H5)2V(5-NH2-phen)]OTf (V1) and molybdenum complex [(η(3)-C3H5)Mo(CO)2(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mo1 complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Šebestová
authors.affiliation: Department of Biological and Biochemical Science, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Havelek
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, 500 38 Hradec Králové, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Řezáčová
authors.affiliation: Institute of Chemistry and Technology of Macromolecular Materials, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Honzíček
authors.affiliation: Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, 500 01 Hradec Králové, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kročová
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic. Electronic address: jaromir.vinklarek@upce.cz.
authors.forename: Jaromír
authors.initials: J
authors.lastname: Vinklárek
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008982:Molybdenum / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014639:Vanadium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014639:Vanadium; D012694:Serine; D008982:Molybdenum; D020169:Caspases
keywords: Apoptosis; Jurkat; MOLT-4; Organometallic compounds; p53