Type

Journal Article

Authors

John F Gilmer
Marek W Radomski
Mark Ledwidge
Despina Bazou
Paula Cantwell
Michael Jones
Maria Jose Santos-Martinez
Iwona Inkielewicz
Shona Harmon
Carlos Medina

Subjects

Pharmacology

Topics
cytology drug effects microscopy phase contrast analogs derivatives chromatography high pressure liquid cell communication cell line tumor platelet aggregation blood platelets humans pharmacology aspirin isosorbide physostigmine niacin flow cytometry isosorbide 5 nicotinate 2 aspirinate drug stability prodrugs

Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin. (2011)

Abstract Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the pharmacological effects of a new group of isosorbide-based aspirin prodrugs on TCIPA. TCIPA was induced in human platelets by mixing with human adenocarcinoma or fibrosarcoma cells under no flow and flow conditions. The release of gelatinases and P-selectin expression during TCIPA were studied by zymography and flow cytometry respectively. Tumour cells caused platelet aggregation. This aggregation resulted in the release of MMP-2 and a significant up-regulation of P-selectin on platelets, indicative of platelet activation. Pharmacological modulation of TCIPA revealed that ST0702, one of the aspirin prodrugs, down-regulated TCIPA while aspirin was ineffective. The deacetylated metabolite of ST0702, 5-nicotinate salicylate (ST0702 salicylate), down-regulated both ADP-stimulated platelet aggregation and TCIPA. Our results show that ST0702 was an effective inhibitor of TCIPA in vitro. Its deacetylated metabolite may contribute to the effects of ST0702 by inhibiting ADP-mediated TCIPA.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

John F Gilmer, Marek W Radomski, Mark Ledwidge, Despina Bazou, Paula Cantwell, Michael Jones, Maria Jose Santos-Martinez, Iwona Inkielewicz, Shona Harmon, Carlos Medina

Experts in our system

1
John Gilmer
Trinity College Dublin
Total Publications: 28
 
2
Marek W Radomski
Trinity College Dublin
Total Publications: 44
 
3
Mark Ledwidge
University College Dublin
Total Publications: 30
 
4
Maria Jose Santos-Martinez
Trinity College Dublin
Total Publications: 29
 
5
Carlos Medina
Trinity College Dublin
Total Publications: 23