Action of antitumoral platinum complexes on in vitro platelet functions.
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.
Dalla Via
L
L
Department of Biological Chemistry, University of Padova, Italy.
Di Noto
V
V
Vidali
M
M
Scomazzon
F
F
Ni
D
D
Deana
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013237:Stereoisomerism; D014783:Viscosity
D000970:Antineoplastic Agents; D001798:Blood Proteins; C034697:transplatin; D012701:Serotonin; D002945:Cisplatin; D002118:Calcium