[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties

Abstract

There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.