Document Detail


BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma.
MedLine Citation:
PMID:  20374272     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The ubiquitin-proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC). METHODS: Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT-test. BSc2118-induced apoptosis was analyzed by annexin-V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays. RESULTS: In OPM-2, RPMI-8226, U266 cell lines and primary MM cells, BSc2118 caused dose-dependent growth inhibitory effects. After 48 h, dose-dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2-M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF-kappaB activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent. CONCLUSION: Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development.
Authors:
Jan Sterz; Christian Jakob; Ulrike Kuckelkorn; Ulrike Heider; Maren Mieth; Lorenz Kleeberg; Martin Kaiser; Peter-M Kloetzel; Orhan Sezer; Ivana von Metzler
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  European journal of haematology     Volume:  85     ISSN:  1600-0609     ISO Abbreviation:  Eur. J. Haematol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8703985     Medline TA:  Eur J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  99-107     Citation Subset:  IM    
Affiliation:
Department of Hematology and Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany. sezer@charite.de; o.sezer@uke.de
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents
Apoptosis / drug effects
Bone Marrow Examination
Butanes / pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Leukocytes, Mononuclear / drug effects
Multiple Myeloma / drug therapy*,  pathology
Oligopeptides / pharmacology*
Proteasome Endopeptidase Complex / antagonists & inhibitors*
Translocation, Genetic
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BSc2118; 0/Butanes; 0/Oligopeptides; EC 3.4.25.1/Proteasome Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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