title: 2'-Ethoxy-5'-methoxy-2-(5-methylthienyl)chalcone inhibits collagen-induced protein tyrosine phosphorylation and thromboxane formation during platelet aggregation and adhesion.
abstract: Subendothelial collagen supports platelet adhesion, activation, and thrombus growth at sites of vascular damage. Previous studies have shown that chalcones possess antiplatelet activity, but their mechanism of action is not fully understood. In this study, a recently synthesized chalcone, 2'-ethoxy-5'-methoxy-2-(5-methylthienyl)chalcone (EMMTC), was used to investigate chalcone effects on platelet aggregation and adhesion. We found that EMMTC potently inhibited collagen-induced platelet aggregation with an IC(50) of 1.01 micromol/l. In contrast, it did not inhibit thrombin- and ADP-induced platelet aggregation. EMMTC could inhibit arachidonic acid (AA)-induced platelet aggregation and collagen- and AA-induced thromboxane B(2) (TXB(2)) formation, suggesting that cyclooxygenase and/or thromboxane synthase were affected during this process. Moreover, EMMTC suppressed collagen-induced protein tyrosine phosphorylation, including phospholipase C-gamma2 (PLC-gamma2), phosphatidylinositol-3 kinase (PI-3K), Src, Fyn and LAT. Strikingly, EMMTC also blocked platelet adhesion to immobilized collagen and convulxin (a snake venom-derived protein that activates platelet glycoprotein VI receptor). The attenuation of phosphorylation of focal adhesion kinase (FAK) was observed during adhesion. Taken together, our results presented here demonstrate that the chalcone derivative EMMTC affects collagen-induced protein tyrosine phosphorylation and TXB(2) formation and functionally blocks collagen-induced platelet aggregation and adhesion.
authors.affiliation: School of Medicine, Fu-Jen Catholic University, Taipei 24205, Taiwan.
authors.forename: Huey-Ming
authors.initials: HM
authors.lastname: Lo
authors.forename: Tur-Fu
authors.initials: TF
authors.lastname: Huang
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Lin
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Peng
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Wu
mesh_terms: D000818:Animals; D002599:Chalcone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D003435:Crotalid Venoms / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D037181:Lectins, C-Type / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000378:metabolism; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism
chemical_list: C545454:2'-ethoxy-5'-methoxy-2-(5-methylthienyl)chalcone; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D013876:Thiophenes; C028890:convulxin; D014443:Tyrosine; D013929:Thromboxane B2; D002599:Chalcone; D003094:Collagen; D011451:Prostaglandin-Endoperoxide Synthases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D013930:Thromboxane-A Synthase