Influence of vincristine, clinically used in cancer therapy and immune thrombocytopenia, on the function of human platelets

Li Ming Lien, Wan Jung Lu, Kuan Hung Lin, Ling Hsuan Kang, Ting Yu Chen, Bo Jung Lin, Yung Chang Lu, Chun Yao Huang, Chun Ming Shih, Hsuan Chen, Yao Chou Tsai, Ray Jade Chen, Joen Rong Sheu

Research output: Contribution to journalArticlepeer-review

Abstract

Vincristine is a clinically used antimicrotubule drug for treating patients with lymphoma. Due to its property of increasing platelet counts, vincristine is also used to treat patients with immune thrombocytopenia. Moreover, antiplatelet agents were reported to be beneficial in thrombotic thrombocytopenic purpura (TTP). Therefore, we investigated the detailed mechanisms underlying the antiplatelet effect of vincristine. Our results revealed that vincristine inhibited platelet aggregation induced by collagen, but not by thrombin, arachidonic acid, and the thromboxane A2 analog U46619, suggesting that vincristine exerts higher inhibitory effects on collagen-mediated platelet aggregation. Vincristine also reduced collagen-mediated platelet granule release and calcium mo-bilization. In addition, vincristine inhibited glycoprotein VI (GPVI) signaling, including Syk, phos-pholipase Cγ2, protein kinase C, Akt, and mitogen-activated protein kinases. In addition, the in vitro PFA-100 assay revealed that vincristine did not prolong the closure time, and the in vivo study tail bleeding assay showed that vincristine did not prolong the tail bleeding time; both findings suggested that vincristine may not affect normal hemostasis. In conclusion, we demonstrated that vincristine exerts antiplatelet effects at least in part through the suppression of GPVI signaling. Moreover, this property of antiplatelet activity of vincristine may provide additional benefits in the treatment of TTP.

Original languageEnglish
Article number5340
JournalMolecules
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Collagen
  • Glycoprotein VI signaling
  • Immune thrombocy-topenia
  • Platelet activation
  • Vincristine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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