| BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma. | |
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MedLine Citation:
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PMID: 20374272 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jan Sterz; Christian Jakob; Ulrike Kuckelkorn; Ulrike Heider; Maren Mieth; Lorenz Kleeberg; Martin Kaiser; Peter-M Kloetzel; Orhan Sezer; Ivana von Metzler |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-31 |
Journal Detail:
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Title: European journal of haematology Volume: 85 ISSN: 1600-0609 ISO Abbreviation: Eur. J. Haematol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8703985 Medline TA: Eur J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 99-107 Citation Subset: IM |
Affiliation:
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Department of Hematology and Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany. sezer@charite.de; o.sezer@uke.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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