Apoptosis induction and inhibition of H-ras overexpression by novel trans-[PtCl2(isopropylamine)(amine′)] complexes

Abstract Hitherto, it has been generally accepted as a paradigm of the biochemical pharmacology of platinum antitumor drugs that a cis configuration of the leaving groups is necessary for antitumor activity of platinum compounds. However, it has been recently observed that certain trans -platinum complexes have both in vitro and in vivo antitumor activity. We previously reported the synthesis, characterization and cytotoxic activity against ras -transformed cells of several trans -[PtCl 2 LL′] complexes where L and L′ are asymmetric aliphatic amines (L=dimethylamine and butylamine, L′=isopropylamine). The results reported in this paper show that the compounds trans -[PtCl 2 (isopropylamine)(dimethylamine)] and trans -[PtCl 2 (isopropylamine)(butylamine)] kill Pam 212- ras cisplatin resistant cells through apoptosis induction. Moreover, Western blot data show that both compounds inhibit overexpression of H- ras oncogene in Pam 212- ras cells. Altogether, these data indicate that, in contrast with cis -DDP, the apoptotic activity of these novel trans -Pt(II) compounds in ras -transformed cells is associated with their ability to abolish ras -overexpression.