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

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)2142-2152
頁數11
期刊Journal of Cellular and Molecular Medicine
22
發行號4
DOIs
出版狀態已發佈 - 四月 1 2018

指紋

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

引用此文

@article{42a7a872a603496daa06c81b057e6945,
title = "Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen-integrin αII bβ3 binding in human platelets",
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.",
keywords = "Antithrombosis, Fibrinogen, Integrin α β, Norcantharidin, Platelet aggregation",
author = "Hsia, {Chih Hsuan} and Lu, {Wan Jung} and Lin, {Kuan Hung} and Chou, {Duen Suey} and Pitchairaj Geraldine and Thanasekaran Jayakuma and Chang, {Nen Chung} and Sheu, {Joen Rong}",
note = "{\circledC} 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.",
year = "2018",
month = "4",
day = "1",
doi = "10.1111/jcmm.13488",
language = "English",
volume = "22",
pages = "2142--2152",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful inhibitor by interfering with fibrinogen-integrin αII bβ3 binding in human platelets

AU - Hsia, Chih Hsuan

AU - Lu, Wan Jung

AU - Lin, Kuan Hung

AU - Chou, Duen Suey

AU - Geraldine, Pitchairaj

AU - Jayakuma, Thanasekaran

AU - Chang, Nen Chung

AU - Sheu, Joen Rong

N1 - © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

KW - Antithrombosis

KW - Fibrinogen

KW - Integrin α β

KW - Norcantharidin

KW - Platelet aggregation

UR - http://www.scopus.com/inward/record.url?scp=85041058355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041058355&partnerID=8YFLogxK

U2 - 10.1111/jcmm.13488

DO - 10.1111/jcmm.13488

M3 - Article

C2 - 29369482

AN - SCOPUS:85041058355

VL - 22

SP - 2142

EP - 2152

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 4

ER -