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: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2003
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| 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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| 245 | 1 | 0 | |a Proteasome inhibitors induce growth inhibition and apoptosis in myeloma cell lines and in human bone marrow myeloma cells irrespective of chromosome 13 deletion |c Ivana Zavrski, Cord Naujokat, Kathrin Niemöller, Christian Jakob, Ulrike Heider, Corinna Langelotz, Claudia Fleissner, Jan Eucker, Kurt Possinger & Orhan Sezer |
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| 520 | |a 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. | ||
| 650 | 4 | |a Antigens, CD34 | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Caspase 3 | |
| 650 | 4 | |a Caspase 7 | |
| 650 | 4 | |a Caspases | |
| 650 | 4 | |a Cell Cycle | |
| 650 | 4 | |a Cell Division | |
| 650 | 4 | |a Chromosome Deletion | |
| 650 | 4 | |a Chromosomes, Human, Pair 13 | |
| 650 | 4 | |a Cysteine Endopeptidases | |
| 650 | 4 | |a Hematopoietic Stem Cells | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Multienzyme Complexes | |
| 650 | 4 | |a Multiple Myeloma | |
| 650 | 4 | |a Proteasome Endopeptidase Complex | |
| 650 | 4 | |a Tumor Cells, Cultured | |
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| 700 | 1 | |a Jakob, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heider, Ulrike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Langelotz, Corinna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fleissner, Claudia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eucker, Jan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Possinger, Kurt |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sezer, Orhan |e VerfasserIn |4 aut | |
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