title: Cytotoxic activity of novel palladium-based compounds on leukemia cell lines.
abstract: Effective treatment methods for human leukemia are under development, but so far none of them have been found to be completely satisfactory. It was recently reported that palladium complexes have significant anticancer activity as well as lower toxicity compared with some clinically used chemotherapeutics. The anticancer activities of two novel palladium(II) complexes, [Pd(sac)(terpy)](sac)·4H2O and [PdCl(terpy)](sac)·2H2O, were tested against three human leukemia cell lines, Jurkat, MOLT-4, and THP-1, in comparison with cisplatin and adriamycin. The cytotoxic effect of the drugs was determined using the MTT assay. Cell death was assessed using fluorescein isothiocyanate-annexin/propidium iodide staining for flow cytometry. Furthermore, p53 phosphorylation, poly(ADP-ribose) polymerase cleavage, and Bax and Bcl-2 mRNA levels were examined to elucidate the mechanism of cell death induction. Both complexes exhibited a significant dose-dependent antigrowth effect in vitro. The complexes predominately induced apoptosis, but necrosis was also observed. In-vitro results have shown that palladium(II) complexes may be regarded as potential anticancer agents for treating human leukemia. Therefore, further analysis to determine the putative mechanism of action and in-vivo studies on animal models are warranted.
authors.affiliation: aDepartment of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia bDepartment of Medical Biochemistry, Faculty of Medicine cDepartment of Chemistry, Faculty of Sciences, Uludag University, Bursa, Turkey.
authors.forename: Maja
authors.initials: M
authors.lastname: Antunovic
authors.forename: Bojana
authors.initials: B
authors.lastname: Kriznik
authors.forename: Engin
authors.initials: E
authors.lastname: Ulukaya
authors.forename: Veysel T
authors.initials: VT
authors.lastname: Yilmaz
authors.forename: Katarina C
authors.initials: KC
authors.lastname: Mihalic
authors.forename: Josip
authors.initials: J
authors.lastname: Madunic
authors.forename: Inga
authors.initials: I
authors.lastname: Marijanovic
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010165:Palladium; D004317:Doxorubicin; D002945:Cisplatin