Pharmacological evaluation of the novel thromboxane modulator BM-567 (II/II). Effects of BM-567 on osteogenic sarcoma-cell-induced platelet aggregation.
Evidence exists that a large number of tumor cells such as osteosarcoma cells stimulate platelet aggregation, which can be an early step in the metastatic processes of these tumors. Thromboxane A(2) (TXA(2)) is released during platelet aggregation, and it has been suggested that this release may be pathogenic for tumor metastasis for several reasons:Some tumors release large amounts of TXA(2) compared to normal tissue.TXA(2) potentiates tumor growth in culture and increases metastasis in animals.TXA(2) is a potent stimulant of platelet aggregation and causes vascular injuries that may promote implantation of tumor cell-platelet aggregates. If TXA(2) participates in tumor metastasis, it may be hypothesized that TXA(2) inhibitors should decrease tumor metastasis. So, we have evaluated the effects of the original TXA(2) synthase inhibitor and TXA(2) receptor antagonist BM-567 on platelet aggregation induced by osteosarcoma cells using MG-63 tumor cells. Results obtained showed that this drug inhibited both MG-63 tumor-cell-induced platelet aggregation and platelet TXA(2) release following the tumor cell stimulation with IC(50) values of 3.04x10(-7) and 2.51x10(-8)M, respectively.
de Leval
X
X
Natural and Synthetic Drugs Research Center, University of Liège, B-4000, Liège, Belgium. xdeleval@ulg.ac.be
Benoit
V
V
Delarge
J
J
Julémont
F
F
Masereel
B
B
Pirotte
B
B
Merville
M P
MP
David
J L
JL
Dogné
J M
JM
D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001859:Bone Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D012516:Osteosarcoma / Q000503:physiopathology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
C434802:BM 567; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013453:Sulfonylurea Compounds; D013930:Thromboxane-A Synthase