Open AccessNorcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen–integrin α II b β 3 binding in human platelets
Author(s) -
Hsia ChihHsuan,
Lu WanJung,
Lin KuanHung,
Chou DuenSuey,
Geraldine Pitchairaj,
Jayakuma Thanasekaran,
Chang NenChung,
Sheu JoenRong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13488
Subject(s) - platelet , integrin , fibrinogen , chemistry , platelet activation , pharmacology , microbiology and biotechnology , receptor , cancer research , biochemistry , immunology , medicine , biology
During platelet activation, fibrinogen binds to its specific platelet receptor, integrin α II b β 3 , thus completing the final common pathway for platelet aggregation. Norcantharidin ( NCTD ) is a promising anticancer agent in China from medicinal insect blister beetle. In this study, we provided the evidence to demonstrate NCTD (0.1–1.0 μM) 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 α II b β 3 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 β 3 , Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin α II b β 3 ‐mediated outside‐in signalling 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, and the other side it possesses powerful antiplatelet activity for treating thromboembolic disorders.