Action of antitumoral platinum complexes on in vitro platelet functions

Abstract

This report presents a comparison of the effects of cis- and trans-diamminedichloroplatinum complexes on in vitro platelet functions. Pretreatment of platelets with cis-platinum (cisplatin) induced a slow, dose-dependent (0.1-0.45 mM), increase in the cytosolic Ca2+ concentration, pleckstrin (47 kDa) phosphorylation and serotonin secretion, as well as a slight shape modification with emission of a few pseudopodia. All these effects were remarkably increased in platelets exposed to trans-platinum (transplatin). The rise in cytosolic Ca2+ concentration and serotonin secretion evoked by stimulation of platelets with thrombin were not significantly influenced by cellular exposure to cis-platinum, whereas they were enhanced and inhibited, respectively, by exposure to trans-platinum. Trans-platinum also inhibited thrombin-promoted platelet aggregation to a greater extent than the cis-isomer. While the viscosity of platelet rich-plasma tended to decrease in the presence of cis-platinum, it tended to increase in the presence of trans-platinum. Taken together, these results indicate that the effects on platelet functions of the efficacious antitumor complex cis-platinum is rather different from that of the inactive complex trans-platinum. Therefore, the in vitro tests of platelet functions employed in this study might provide an index of antitumor drug toxicity and serve as a preliminary indicator of therapeutic efficacy.