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

Emmanuel Ampofo1, Thomas Später2, Isabelle Müller3

  • 1Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany. emmanuel.ampofo@uks.eu.

Marine Drugs
|November 17, 2015
PubMed
Abstract

Insights

The marine compound fascaplysin inhibits platelet activation and aggregation, reducing thrombus formation and bleeding time in mice. This demonstrates its novel anti-thrombotic properties.

Area of Science:

  • Pharmacology
  • Hematology
  • Marine Biotechnology

Background:

  • Fascaplysin, a marine-derived kinase inhibitor, targets the PI3K pathway implicated in cancer.
  • The PI3K pathway is crucial for platelet signaling and thrombosis.
  • This study investigates fascaplysin's impact on thrombosis due to its known pathway interactions.

Purpose of the Study:

  • To evaluate the anti-thrombotic effects of fascaplysin.
  • To determine fascaplysin's influence on platelet activation, aggregation, and thrombus formation in vivo.
  • To explore a novel application of fascaplysin beyond its known kinase inhibitory activities.

Main Methods:

  • Flow cytometry was used to analyze platelet activation, aggregation, and platelet-leukocyte aggregate (PLA) formation.
  • In vivo thrombosis was assessed using a mouse dorsal skinfold chamber model with photochemical induction.
  • Tail-vein bleeding time was measured to evaluate hemostatic effects.

Main Results:

  • Fascaplysin reduced glycoprotein (GP)IIb/IIIa activation and platelet aggregation in response to various agonists.
  • Fascaplysin decreased PLA formation with PMA stimulation but not with PAR-1-AP or ADP.
  • In vivo, fascaplysin significantly prolonged vessel occlusion time and increased bleeding time in mice.

Conclusions:

  • Fascaplysin exhibits significant anti-thrombotic activity.
  • This anti-thrombotic effect represents a new facet of fascaplysin's diverse biological actions.
  • Fascaplysin shows potential as a therapeutic agent for thrombotic disorders.

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