Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions

被引：9

作者：

Bulatovic, Mirna ^{[1
]}

Kaluderovic, Milena R. ^{[2
]}

Mojic, Marija ^{[1
]}

Zmejkovski, Bojana B. ^{[3
]}

Hey-Hawkins, Evamarie ^{[4
]}

Vidakovic, Melita ^{[5
]}

Grdovic, Nevena ^{[5
]}

Kaluderovic, Goran N. ^{[4
,6
]}

Mijatovic, Sanja ^{[1
]}

Maksimovic-Ivanic, Danijela ^{[1
]}

机构：

[1] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Dept Immunol, Belgrade 11060, Serbia

[2] Univ Hosp Leipzig, Dept Oral Maxillary Facial & Reconstruct Plast Su, D-04103 Leipzig, Germany

[3] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Belgrade 11000, Serbia

[4] Univ Leipzig, Inst Inorgan Chem, D-04103 Leipzig, Germany

[5] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Dept Mol Biol, Belgrade 11060, Serbia

[6] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, D-06120 Halle, Saale, Germany

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2015年 / 760卷

关键词：

Platinum(IV) complex; Cisplatin; ATP depletion; Mitochondrial collapse; Oxidative stress; Hypoxic conditions; PLATINUM(IV) COMPLEXES; ANTICANCER ACTIVITY; CELL-LINES; CISPLATIN; LIGANDS; SATRAPLATIN; APOPTOSIS; DEATH; CYTOTOXICITY; RESISTANCE;

D O I：

10.1016/j.ejphar.2015.04.012

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

(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.

引用

页码：136 / 144

页数：9

共 62 条

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