| Azaphenylalanine-based serine protease inhibitors induce caspase-mediated apoptosis. | |
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MedLine Citation:
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PMID: 19032950 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Molecules regulating cell death constitute prominent therapeutic targets. The pro-apoptotic role of serine protease inhibitors prompted us to search for novel modulators of this process. We have tested some recently synthesized antithrombotic compounds for their potential to induce apoptotic cell death. Cell based analyses revealed that inhibitors built on the azaphenylalanine scaffold are, for B-cell lymphoma cells, severely cytotoxic, while other compounds tested were moderate or non-cytotoxic. These inhibitors induced the time and concentration dependent biochemical and morphological characteristics of apoptosis, such as DEVDase activation, loss of mitochondrial membrane potential, nuclear degradation and genomic DNA fragmentation. Most of the inhibitors proved to be selective for thrombin, with inhibition constants (K(i)) in the nanomolar range. However, they could also inhibit at least one additional serine protease (trypsin, chymotrypsin and/or coagulation factor X) with K(i) values in the nanomolar or low micromolar range. These serine protease inhibitors constitute novel apoptosis inducing compounds in B-cell lymphoma cells. |
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Authors:
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Teja Celhar; Tina Batista Napotnik; Ales Obreza; Anamarija Zega; Petra Stefanic Anderluh; Danijel Kikelj; Irena Mlinaric-Rascan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-12 |
Journal Detail:
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Title: European journal of pharmacology Volume: 602 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-10-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 15-22 Citation Subset: IM |
Affiliation:
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University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Caspases / metabolism* Cell Line, Tumor Humans Lymphoma, B-Cell / metabolism, pathology Phenylalanine / analogs & derivatives*, pharmacology Serine Proteinase Inhibitors / chemistry*, pharmacology* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Serine Proteinase Inhibitors; 0/azaphenylalanine; 63-91-2/Phenylalanine; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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