The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity

Marine Drugs

Emmanuel Ampofo³  Thomas Später³  Isabelle Müller²  Hermann Eichler²  Michael D. Menger³  Matthias W. Laschke³  Vitor H. Pomin¹ 

[1] Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany;;Institute for Hemostasiology and Transfusion Medicine, Saarland University, 66421 Homburg/Saar, Germany; E-Mails:;Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany; E-Mails:

关键词: fascaplysin;    thrombosis;    platelets;    GPIIb/IIIa;    P-selectin;    leukocytes;    CD11b;    dorsal skinfold chamber;   

DOI  :  10.3390/md13116774

来源: mdpi

【 摘 要 】

Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.