Leukemia, 2009-08, Vol.23 (8), p.1507-1514
2009
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- Autor(en) / Beteiligte
- Titel
- The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia lymphoma cells apoptosis
- Ist Teil von
- Leukemia, 2009-08, Vol.23 (8), p.1507-1514
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Interactions between inhibitors of the proteasome and histone deacetylases have been examined in human T-leukemia/lymphoma cells both in vitro and in vivo . Co-exposure of cells to bortezomib and suberoylanilide hydroxamic acid (SAHA) synergistically induces T-leukemia/lymphoma cells to undergo apoptosis, consistent with a significant increase in mitochondrial injury and caspase activation. These events are accompanied by inhibition of cyto-protective signaling pathways, including the nuclear factor (NF)-κB, Raf-1/mitogen-induced extracellular kinase (MEK)/extracellular signal-related kinase (ERK) and AKT pathways, and activation of stress-related cascades, including the stress-activated kinases c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK). Moreover, bortezomib in conjunction with SAHA efficiently induces apoptosis of primary T-leukemia/lymphoma cells and inhibits tumor growth in a murine xenograft model established with subcutaneous injection of Jurkat cells. Taken together, these findings confirm the synergistic anti-tumor effect of the proteasome and histone deacetylase inhibitors, and provide an insight into the future clinical applications of bortezomib–SAHA combining regimen in treating T-cell malignancies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0887-6924eISSN: 1476-5551DOI: 10.1038/leu.2009.41Titel-ID: cdi_proquest_miscellaneous_21168529
- Format
- –
- Schlagworte
- Acids, AKT protein, Animals, Anticancer properties, Apoptosis, Apoptosis - drug effects, Biological and medical sciences, Boronic Acids - pharmacology, Bortezomib, c-Jun protein, Cancer Research, Care and treatment, Caspase, Cell Line, Tumor - drug effects, Cell Line, Tumor - pathology, Cells, Critical Care Medicine, Drug Synergism, Extracellular signal-regulated kinase, Genomics, Hematologic and hematopoietic diseases, Hematology, Histone deacetylase, Histone Deacetylase Inhibitors, Histones, Humans, Hydroxamic acid, Hydroxamic Acids - pharmacology, Inhibitors, Intensive, Internal Medicine, Intracellular Signaling Peptides and Proteins - antagonists & inhibitors, Intracellular Signaling Peptides and Proteins - physiology, JNK protein, Jurkat Cells - drug effects, Jurkat Cells - enzymology, Jurkat Cells - transplantation, Kinases, Leukemia, Leukemia, T-Cell - drug therapy, Leukemia, T-Cell - enzymology, Leukemia, T-Cell - pathology, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, Lymphocytes T, Lymphoma, Lymphoma, T-Cell - enzymology, Lymphoma, T-Cell - pathology, MAP kinase, Medical sciences, Medicine, Medicine & Public Health, Mice, Mice, Nude, Mitochondria, Neoplasm Proteins - antagonists & inhibitors, Oncology, original-article, Physiological aspects, Protease Inhibitors - pharmacology, Proteasome Inhibitors, Protein kinase, Protein Kinases - physiology, Pyrazines - pharmacology, Raf protein, Signal Transduction - drug effects, T cells, Transcription factors, Ubiquitin-proteasome system, Xenograft Model Antitumor Assays, Xenografts, Xenotransplantation