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Proteasome inhibitors induce growth inhibition and apoptosis in myeloma cell lines and in human bone marrow myeloma cells irrespective of chromosome 13 deletion

PURPOSE: In this study, we investigated the effects of cell-permeable proteasome inhibitors MG-132, MG-262, PSI, and lactacystin on multiple myeloma cell lines OPM-2, U266, RPMI 8226-S, freshly isolated plasma cells with or without deletion of chromosome 13 from patients with multiple myeloma and pl...

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Main Authors: Zavrski, Ivana (Author) , Naujokat, Cord (Author) , Niemöller, Kathrin (Author) , Jakob, Christian (Author) , Heider, Ulrike (Author) , Langelotz, Corinna (Author) , Fleissner, Claudia (Author) , Eucker, Jan (Author) , Possinger, Kurt (Author) , Sezer, Orhan (Author)
Format: Article (Journal)
Language:English
Published: 2003
In: Journal of cancer research and clinical oncology
Year: 2003, Volume: 129, Issue: 7, Pages: 383-391
ISSN:1432-1335
DOI:10.1007/s00432-003-0454-6
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00432-003-0454-6
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Author Notes:Ivana Zavrski, Cord Naujokat, Kathrin Niemöller, Christian Jakob, Ulrike Heider, Corinna Langelotz, Claudia Fleissner, Jan Eucker, Kurt Possinger & Orhan Sezer
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Summary:PURPOSE: In this study, we investigated the effects of cell-permeable proteasome inhibitors MG-132, MG-262, PSI, and lactacystin on multiple myeloma cell lines OPM-2, U266, RPMI 8226-S, freshly isolated plasma cells with or without deletion of chromosome 13 from patients with multiple myeloma and plasma cell leukemia, and CD34+ human hematopoietic stem cells. The effects of proteasome inhibitors on cell cycle progression, cell growth, and apoptosis were determined. METHODS: MTT-assay was used to examine the cytotoxicity, and annexin-V staining to quantify apoptosis. Cell cycle analyses were performed using 7-ADD and Ki-67 staining by flow cytometry. RESULTS: PSI was the most potent proteasome inhibitor among those tested with a half maximal cytotoxicity (IC(50)) of 5.7 nM, followed by MG-262, MG-132, and lactacystin. Growth inhibition occurred irrespective of chromosome 13 status. Cell cycle arrest occurred in a dose- and time-dependent manner. Low, subapoptotic dosages led to a partial loss of Ki-67 antigen, whereas apoptotic dosages led to reduced Ki-67 levels. Apoptosis was partially dependent on activation of caspase-3, since Ac-DEVD-cho, a caspase-3 inhibitor, could reduce apoptosis significantly. The cytotoxicity of the four proteasome inhibitors tested was significantly lower in human hematopoietic stem cells than in myeloma cells. CONCLUSIONS: Our results show that proteasome inhibitors induce time- and dose-dependent cell cycle alterations, growth inhibition, and apoptosis in human myeloma cells irrespective of chromosome 13 deletion.
Item Description:Gesehen am 19.02.2021
Physical Description:Online Resource
ISSN:1432-1335
DOI:10.1007/s00432-003-0454-6

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