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

研究成果: 雜誌貢獻文章同行評審

摘要

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.

原文英語
文章編號5340
期刊Molecules
26
發行號17
DOIs
出版狀態已發佈 - 九月 2021

ASJC Scopus subject areas

  • 分析化學
  • 化學(雜項)
  • 分子醫學
  • 藥學科學
  • 藥物發現
  • 物理與理論化學
  • 有機化學

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