Effects of mitoxantrone and bisantrene on platelet aggregation and prostaglandin/thromboxane biosynthesis in vitro.
The effects of mitoxantrone and bisantrene on agonist-stimulated platelet aggregation, prostaglandin E2 and thromboxane B2 production were examined and results compared with those produced by indomethacin and acetylsalicylic acid. Both mitoxantrone and bisantrene effectively inhibited collagen-, ADP-, and epinephrine-stimulated platelet aggregation. Collagen (0.54 microgram/ml)-stimulated platelet aggregation was inhibited by 50% at 60 microM mitoxantrone and 8 microM bisantrene. The concentration of drug required for inhibition of platelet aggregation varied inversely with the level of collagen stimulus employed. Mitoxantrone and bisantrene inhibited both the first and second phase of epinephrine-stimulated platelet aggregation. Complete inhibition of the second wave of aggregation was obtained at greater than 160 microM mitoxantrone and 16 microM bisantrene. Mitoxantrone is comparable in potency to acetylsalicylic acid which inhibited the second wave of epinephrine-stimulated aggregation 50% at 160 microM, whereas bisantrene may be compared to indomethacin which produced complete inhibition of aggregation at 16 microM. Production of PGE2 and TXB2 in epinephrine-stimulated platelets was inhibited by both drugs with 50% inhibition of PGE2 production occurring at 12 microM mitoxantrone and 3 microM bisantrene. Thromboxane B2 production was inhibited by 50% at 10 microM mitoxantrone and 5 microM bisantrene. Indomethacin inhibited PGE2 and TXB2 production 50% at 4 microM. Thus mitoxantrone and bisantrene inhibit platelet aggregation and prostaglandin production which may be of significance in metastasis and in prostaglandin-mediated physiologic and immune responses.
Frank
P
P
Novak
R F
RF
D000328:Adult; D000873:Anthracenes / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008942:Mitoxantrone / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis*
D000873:Anthracenes; D011453:Prostaglandins; D011458:Prostaglandins E; D013931:Thromboxanes; C031404:bisantrene; D013929:Thromboxane B2; D003094:Collagen; D008942:Mitoxantrone; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin; D004837:Epinephrine