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

Abstract

(O,O'-Diisobutyl-ethylenediamine-N,N'-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu2eddp)], 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(iBu2eddp)] 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.

• Authors: Mirna Bulatović, Milena R Kaluđerović, Marija Mojić, Bojana B Zmejkovski, Evamarie Hey-Hawkins, Melita Vidaković, Nevena Grdović, Goran N Kaluđerović, Sanja Mijatović, Danijela Maksimović-Ivanić
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 760 Pg. 136-44 (Aug 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25912798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• Antineoplastic Agents
• Platinum Compounds
• platinum tetrachloride

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects, physiology)
• Cell Hypoxia (drug effects, physiology)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Mice
• NIH 3T3 Cells
• Platinum Compounds (chemistry, pharmacology)