PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells
| Autor: | Mario Petrini, Luisa Trombi, Simone Pacini, Enrico Orciuolo, Simona Piaggi, A. Capodanno, Rita Fazzi, Alessandro Casini, Letizia Mattii, Martina Canestraro, Paola Collecchi, Sara Galimberti, Paolo Simi, B. Battolla, F. Veroni |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Cellular differentiation Gene Expression Apoptosis NF-κB Bortezomib chemistry.chemical_compound Leukemia Megakaryoblastic Acute hemic and lymphatic diseases Tumor Leukemia Cell Cycle Cell Differentiation Hematology Cell cycle Protein-Serine-Threonine Kinases Boronic Acids Oncology Pyrazines Drug medicine.drug Megakaryoblastic Genes Wilms Tumor HL60 Antineoplastic Agents Protein Serine-Threonine Kinases Megakaryoblastic leukemia Acute Biology Wilms Tumor Cell Line Dose-Response Relationship Myeloproliferative Disorders Cell Line Tumor medicine Humans Protease Inhibitors PS-341 WT1 Cell Proliferation Dose-Response Relationship Drug Primary Myelofibrosis Cell growth Genes chemistry Proteasome inhibitor Cancer research |
| Zdroj: | Leukemia Research. 32:103-112 |
| ISSN: | 0145-2126 |
| Popis: | PS-341 (Bortezomib) is a dipeptide boronic acid proteasome inhibitor with antitumor activity that induces apoptosis in different human cancer cell lines. We investigated effects of PS-341 (Bortezomib) on cell proliferation, cell cycle progression, induction of apoptosis and differentiation in a megakaryoblastic (MO7-e) cell line. PS-341 was able to retain NF-κB in the cytoplasm and inhibit cell growth (IC 50 = 22.5 nM), in a dose/time-dependent way. This anti-proliferative activity resulted to be lineage-specific, because other leukemic cell lines (KG1a, K562/R7, HL60/DNR) were unaffected by the PS-341 treatment. Moreover, PS-341 in MO7-e induced a significant pro-apoptotic effect from 10 nM concentration (40% versus 12% in the control, p On the other hand, at lower concentration (5 nM), Bortezomib blocked cell cycle in the G2 phase. Finally, this compound was able to down-regulate WT1 expression. No significant effects on cell differentiation were found. Because a spontaneous NF-κB activation has been reported in megakaryocytes from patients affected by myeloproliferative disorders, Bortezomib would so be an attractive therapeutic tool for these malignancies, including essential thrombocythemia or idiopathic myelofibrosis. Preliminary data show an inhibiting activity of Bortezomib in the megakaryocytic colonies formation. Finally, also down-regulation of the WT1 gene Bortezomib-driven could be relevant, because of the role that this gene would play in the pathogenesis of acute and chronic myeloproliferative disorders. |
| Databáze: | OpenAIRE |
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