Improved in vitro antitumor potential of (O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplati num(IV) complex under normoxic and hypoxic conditions
2015
Authors:
Bulatović, Mirna Z.Kaluderovic, Milena R.
Mojić, Marija
Zmejkovski, Bojana B.
Hey-Hawkins, Evamarie
Vidaković, Melita
Grdović, Nevena
Kaluđerović, Goran N.
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplati
num(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.
Keywords:
Platinum(IV) complex; Cisplatin; Mitochondrial collapse; Oxidative stress; Hypoxic conditionsSource:
European Journal of Pharmacology, 2015, 760, 136-144
DOI: 10.1016/j.ejphar.2015.04.012
ISSN: 1879-0712