Cellular uptake, DNA binding and apoptosis induction of cytotoxic trans-[PtCl2(N,N-dimethylamine)(isopropylamine)] in A2780cisR ovarian tumor cells

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)(isopropylamine)] is partially inactivated by intracellular levels of glutathione. The results suggest that circumvention of cisplatin resistance by trans-[PtCl2(N,N-dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.