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 A₂ (TXA₂) is released during platelet aggregation, and it has been suggested that this release may be pathogenic for tumor metastasis for several reasons: 1. Some tumors release large amounts of TXA₂ compared to normal tissue. 2. TXA₂ potentiates tumor growth in culture and increases metastasis in animals. 3. TXA₂ is a potent stimulant of platelet aggregation and causes vascular injuries that may promote implantation of tumor cell-platelet aggregates. If TXA₂ participates in tumor metastasis, it may be hypothesized that TXA₂ inhibitors should decrease tumor metastasis. So, we have evaluated the effects of the original TXA₂ synthase inhibitor and TXA₂ 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 TXA₂ release following the tumor cell stimulation with IC₅₀ values of 3.04 x 10^-7 and 2.51 x 10^-8 M, respectively.