title: Novel platinum(IV) complexes induce rapid tumor cell death in vitro.
abstract: The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Belgrade, Serbia and Montenegro.
authors.forename: Goran N
authors.initials: GN
authors.lastname: Kaludjerović
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljković
authors.forename: Miljana
authors.initials: M
authors.lastname: Momcilović
authors.forename: Vesna M
authors.initials: VM
authors.lastname: Djinović
authors.forename: Marija
authors.initials: M
authors.lastname: Mostarica Stojković
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Sabo
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajković
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D009336:Necrosis; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D018384:Oxidative Stress; D010984:Platinum / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D009944:Organoplatinum Compounds; D010984:Platinum