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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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Hauptverfasser: Zavrski, Ivana (VerfasserIn) , Naujokat, Cord (VerfasserIn) , Niemöller, Kathrin (VerfasserIn) , Jakob, Christian (VerfasserIn) , Heider, Ulrike (VerfasserIn) , Langelotz, Corinna (VerfasserIn) , Fleissner, Claudia (VerfasserIn) , Eucker, Jan (VerfasserIn) , Possinger, Kurt (VerfasserIn) , Sezer, Orhan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2003
In: Journal of cancer research and clinical oncology
Year: 2003, Jahrgang: 129, Heft: 7, Pages: 383-391
ISSN:1432-1335
DOI:10.1007/s00432-003-0454-6
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00432-003-0454-6
Volltext
Verfasserangaben:Ivana Zavrski, Cord Naujokat, Kathrin Niemöller, Christian Jakob, Ulrike Heider, Corinna Langelotz, Claudia Fleissner, Jan Eucker, Kurt Possinger & Orhan Sezer
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 19.02.2021
Beschreibung:Online Resource
ISSN:1432-1335
DOI:10.1007/s00432-003-0454-6

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