Pharmacological evaluation of the novel thromboxane modulator BM-567 (II/II). Effects of BM-567 on osteogenic sarcoma-cell-induced platelet aggregation

X. De Leval, V. Benoit, J. Delarge, F. Julémont, B. Masereel, B. Pirotte, M. P. Merville, J. L. David, J. M. Dogné

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)55-59
Number of pages5
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume68
Issue number1
DOIs
Publication statusPublished - 1 Jan 2003

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