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Montero, EL ; Pérez, JM ; Schwartz, A ; Fuertes, MA ; Malinge, JM ; Alonso, C ; Leng, M ; Navarro-Ranninger, C

Apoptosis induction and DNA interstrand cross-link formation by cytotoxic trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2) : cross-linking between d(G) and complementary d(C) within oligonucleotide duplexes.

Chembiochem 3 (1) 61-67

par Administrateur - publié le

Abstract :

We have investigated the cytotoxic activity, the induction of apoptosis, and the interstrand cross-linking efficiency in the A2780cisR ovarian tumor cell line, after replacement of the two NH3 nonleaving groups in trans-[PtCl2(NH3)2] (trans-DDP) by dimethylamine and isopropylamine. The data show that trans-[PtCl2(NH(CH)2)(NHCH(CH3)2)] is able to circumvent resistance to cis-[PtCl2(NH3)2] (cis-DDP, cisplatin) in A2780cisR cells. In fact, trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] shows a cytotoxic potency higher than that of cis-DDP and trans-DDP, with the mean IC50 values being 11, 58, and 300 microM, respectively. In addition, at equitoxic doses (concentrations of the platinum drugs equal to their IC50 values) and after 24 hours of drug treatment, the level of induction of apoptosis by trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] is twice that produced by cis-DDP.