Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen-integrin αII bβ3 binding in human platelets

Chih Hsuan Hsia, Wan Jung Lu, Kuan Hung Lin, Duen Suey Chou, Pitchairaj Geraldine, Thanasekaran Jayakuma, Nen Chung Chang, Joen Rong Sheu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αII bβ3, 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 αII bβ3 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 β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αII bβ3-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.

Original languageEnglish
Pages (from-to)2142-2152
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Fingerprint

norcantharidin
Integrins
Fibrinogen
Blood Platelets
Clot Retraction
Bleeding Time
P-Selectin
Fluorescein-5-isothiocyanate
Beetles
Platelet Activation
Blister
Platelet Count
Platelet Aggregation
Human Activities
Antineoplastic Agents
Insects

Keywords

  • Antithrombosis
  • Fibrinogen
  • Integrin α β
  • Norcantharidin
  • Platelet aggregation

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen-integrin αII bβ3 binding in human platelets. / Hsia, Chih Hsuan; Lu, Wan Jung; Lin, Kuan Hung; Chou, Duen Suey; Geraldine, Pitchairaj; Jayakuma, Thanasekaran; Chang, Nen Chung; Sheu, Joen Rong.

In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 4, 01.04.2018, p. 2142-2152.

Research output: Contribution to journalArticle

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abstract = "During platelet activation, fibrinogen binds to its specific platelet receptor, integrin αII bβ3, 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 αII bβ3 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 β3, Src and FAK in platelets spreading on immobilized fibrinogen. These results indicate that NCTD restricts integrin αII bβ3-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.",
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AU - Lin, Kuan Hung

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AU - Chang, Nen Chung

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