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Novel platinum(IV) complexes induce rapid tumor cell death in vitro
Author(s) -
Kaludjerović Goran N.,
Miljković Djordje,
Momcilović Miljana,
Djinović Vesna M.,
Stojković Marija Mostarica,
Sabo Tibor J.,
Trajković Vladimir
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21080
Subject(s) - cisplatin , cytotoxicity , fibrosarcoma , chemistry , programmed cell death , in vitro , apoptosis , cytotoxic t cell , platinum , cancer research , toxicity , necrosis , pharmacology , denticity , stereochemistry , biochemistry , chemotherapy , medicine , pathology , metal , organic chemistry , catalysis
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. © 2005 Wiley‐Liss, Inc.