Kaludjerović, Goran N. (8622940700)Goran N. (8622940700)KaludjerovićMiljković, Djordje (7006524033)Djordje (7006524033)MiljkovićMomcilović, Miljana (14050637900)Miljana (14050637900)MomcilovićDjinović, Vesna M. (8627424300)Vesna M. (8627424300)DjinovićStojković, Marija Mostarica (6701741422)Marija Mostarica (6701741422)StojkovićSabo, Tibor J. (7004201321)Tibor J. (7004201321)SaboTrajković, Vladimir (7004516866)Vladimir (7004516866)Trajković2025-06-132025-06-132005https://doi.org/10.1002/ijc.21080https://www.scopus.com/inward/record.uri?eid=2-s2.0-22244452610&doi=10.1002%2fijc.21080&partnerID=40&md5=12a88e0cf964e8a89a5386c8e81a477bhttps://remedy.med.bg.ac.rs/handle/123456789/10993The 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. © 2005 Wiley-Liss, Inc.ApoptosisCisplatinNecrosisOxidative stressPlatinum(IV)