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Apoptosis induction and inhibition of H-ras overexpression by novel trans-[PtCl2(isopropylamine)(amine′)] complexes1This work was presented at the 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, held in Oxford, UK, 28–31 March 1999.1

1999; Elsevier BV; Volume: 77; Issue: 1-2 Linguagem: Inglês

10.1016/s0162-0134(99)00143-9

1873-3344

J.M. Trigo Perez, Eva I. Montero, Ana María González Noya, Amparo Álvarez-Valdés, C. Alonso, Carmen Navarro‐Ranninger,

Click Chemistry and Applications

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-[PtCl2LL′] 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-[PtCl2(isopropylamine)(dimethylamine)] and trans-[PtCl2(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.