NCTD, a clinical used chemotherapeutic agent, acts as a powerful inhibitor of platelet activation

[Speaker] Joen Rong Sheu:1
[Co-author] Chih Hsuan Hsia:1
1:Graduate Institute of Medical Sciences, Taipei Medical University, Taiwan

During platelet activation, fibrinogen binds to its specific platelet receptor, integrin, thus completing the final common pathway for platelet aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from medicinal insect blister beetle. In the current study, we provided the evidences to demonstrate NCTD possesses very powerful antiplatelet activity in human platelets, nevertheless it had no effects on surface P selectin expression and only slight inhibition on ATP release reaction in activated platelets. Moreover, NCTD markedly hindered integrin activation by interfering with the binding of FITC-labelled PAC-1. It also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated phosphorylation of proteins such as integrin , Src, and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin-mediated outside-in signaling in human platelets. Besides, NCTD substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation and prolonged the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a chemotherapeutic agent for cancer treatment, the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders.
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