The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity
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, pla...
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| Format: | Article |
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MDPI AG
2015-11-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/11/6774 |
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| author | Emmanuel Ampofo Thomas Später Isabelle Müller Hermann Eichler Michael D. Menger Matthias W. Laschke |
| author_facet | Emmanuel Ampofo Thomas Später Isabelle Müller Hermann Eichler Michael D. Menger Matthias W. Laschke |
| author_sort | Emmanuel Ampofo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T22:32:10Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T22:32:10Z |
| publishDate | 2015-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-82f9d6b1f0834c6190ff6c0c854690532022-12-22T03:59:20ZengMDPI AGMarine Drugs1660-33972015-11-0113116774679110.3390/md13116774md13116774The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic ActivityEmmanuel Ampofo0Thomas Später1Isabelle Müller2Hermann Eichler3Michael D. Menger4Matthias W. Laschke5Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Hemostasiology and Transfusion Medicine, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Hemostasiology and Transfusion Medicine, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyBackground: 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.http://www.mdpi.com/1660-3397/13/11/6774fascaplysinthrombosisplateletsGPIIb/IIIaP-selectinleukocytesCD11bdorsal skinfold chamber |
| spellingShingle | Emmanuel Ampofo Thomas Später Isabelle Müller Hermann Eichler Michael D. Menger Matthias W. Laschke The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity Marine Drugs fascaplysin thrombosis platelets GPIIb/IIIa P-selectin leukocytes CD11b dorsal skinfold chamber |
| title | The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity |
| title_full | The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity |
| title_fullStr | The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity |
| title_full_unstemmed | The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity |
| title_short | The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity |
| title_sort | marine derived kinase inhibitor fascaplysin exerts anti thrombotic activity |
| topic | fascaplysin thrombosis platelets GPIIb/IIIa P-selectin leukocytes CD11b dorsal skinfold chamber |
| url | http://www.mdpi.com/1660-3397/13/11/6774 |
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