期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 760, 期 -, 页码 136-144出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2015.04.012
关键词
Platinum(IV) complex; Cisplatin; ATP depletion; Mitochondrial collapse; Oxidative stress; Hypoxic conditions
资金
- Ministry of Science and Technological Development of the Republic of Serbia [173013, 173020, 172035]
- SMWK [33707045]
- SAB (ESF) [100147954]
- Free State of Saxony [100099597]
(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu(2)eddp)]. shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation. Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu(2)eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient. (C) 2015 Published by Elsevier B.V.
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