PRECLINICAL REPORTSCytotoxic activity of novel palladium-based compounds on leukemia cell linesAntunovic, Majaa; Kriznik, Bojanaa; Ulukaya, Enginb; Yilmaz, Veysel T.c; Mihalic, Katarina C.a; Madunic, Josipa; Marijanovic, IngaaAuthor Information 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 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.anti-cancerdrugs.com). Correspondence to Inga Marijanovic, PhD, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia Tel: +385 (0)1 4606 275; fax: +385 (0)1 4606 286; e-mail: email@example.com Received July 10, 2014 Accepted August 24, 2014 Anti-Cancer Drugs: February 2015 - Volume 26 - Issue 2 - p 180-186 doi: 10.1097/CAD.0000000000000174 Buy SDC Metrics 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. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.