Cellular Uptake, DNA Binding and Apoptosis Induction of Cytotoxic Trans-[PtCl(2)(N,N-dimethylamine)(Isopropylamine)] in A2780cisR Ovarian Tumor Cells.

Abstract

Trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] is a novel trans-platinum compound that shows cytotoxic activity in several cisplatin resistant cell lines. The aim of this paper was to analyse, by means of molecular cell biology techniques and total reflection X-ray fluorescence (TXRF), the cytotoxic activity, the induction of apoptosis, the cellular uptake and the DNA binding of trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in the cisplatin resistant cell line A2780cisR. The results show that this drug is more cytotoxic and induces a higher amount of apoptotic cells than cisplatin in A2780cisR cells. However, the intracellular accumulation and extent of binding to DNA of trans-[PtCl(2)(N,N-dimethylamine)( isopropylamine)] is lower than that of cis-DDP. Moreover, trans-[PtCl(2)(N,N-dimethylamine)(isopropylaminae)] is partially inactivated by intracellular levels of glulathione. The result suggest that circumvention of ciplatin resistance by trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.

• Authors: J M Pérez, E I Montero, A G Quiroga, M A Fuertes, C Alonso, C Navarro-Ranninger
• Journal: Metal-based drugs (Met Based Drugs) Vol. 8 Issue 1 Pg. 29-37 ( 2001) ISSN: 0793-0291 [Print] United States
• PMID: 18475973 (Publication Type: Journal Article)