Cellular Uptake, DNA Binding and Apoptosis Induction of Cytotoxic Trans-[PtCl2(N,N-dimethylamine)(Isopropylamine)] in A2780cisR Ovarian Tumor Cells

José M Pérez,Adoración G Quiroga,Carlos Alonso,Miguel A Fuertes,Eva I Montero,Carmen Navarro-Ranninger

doi:10.1155/mbd.2001.29

José M Pérez, Adoración G Quiroga + Show 4 more

Open Access

https://doi.org/10.1155/mbd.2001.29

Copy DOI

Abstract

Trans-[PtCl2(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-[PtCl2(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-[PtCl2(N,N-dimethylamine)( isopropylamine)] is lower than that of cis-DDP. Moreover, trans-[PtCl2(N,N-dimethylamine)(isopropylaminae)] is partially inactivated by intracellular levels of glulathione. The result suggest that circumvention of ciplatin resistance by trans-[PtCl2(N,N-dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.

Highlights

Cisplatin [cis-diammmedichloroplatinum (II), cis-DDP] is one of the most widely used drugs in the treatment of cancer
The results reported in this paper indicate that trans-[PtCl2(N,N-dimethylamine)(isopropylamine)] is able to overcome cisplatin-resistance in A2780cisR cells through apoptoss induction
The aim of the present study was to investigate whether the cellular uptake, the reaction with GSH and the level ot platinum binding to DNA of trans-[PtC12(N,N-dimethylamine)(isopropylamine)] may help to understand the mechamsm(s) by which this drug overcomes cisplatin resistance

Summary

Introduction

Cisplatin [cis-diammmedichloroplatinum (II), cis-DDP] is one of the most widely used drugs in the treatment of cancer. It shows remarkable activity alone or in combination with other drugs in the treatment of several tumors, including those of the lung, ovary, testes and bladder [1, 2]. The success of cis-DDP as an antiturnor drug has been attributed to different factors, including penetration of the cellular membrane, accumulation in the tumor cell. The cisDDP resistance may take place at various levels, including cellular accumulation, interaction with glutathione (GSH) and/or metallothioneins, DNA repair and defective apoptotic program [8]

Objectives

Methods

Results