TRAIL is a potent inducer of apoptosis in myeloma cells derived from multiple myeloma patients and is not cytotoxic to hematopoietic stem cells
| Autor: | Y Gazitt |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Programmed cell death Time Factors Paclitaxel CD34 Antigens CD34 Apoptosis Methylcellulose Biology Transfection Fas ligand Colony-Forming Units Assay TNF-Related Apoptosis-Inducing Ligand NAD+ Nucleosidase Antigens CD Tumor Cells Cultured Humans Cytotoxic T cell ADP-ribosyl Cyclase Cells Cultured Membrane Glycoproteins Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Hematology Flow Cytometry Hematopoietic Stem Cells ADP-ribosyl Cyclase 1 Antigens Differentiation Genes bcl-2 Haematopoiesis Proto-Oncogene Proteins c-bcl-2 Oncology Cell culture Immunology Cancer research Leukocyte Common Antigens Stem cell Apoptosis Regulatory Proteins Multiple Myeloma Cell Division |
| Zdroj: | Leukemia. 13:1817-1824 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2401501 |
| Popis: | TRAIL, the ligand for the newly discovered DR-4 and DR-5 receptor, is a member of the TNF family of death signal transduction proteins with a mechanism of cell death similar to that of Fas and Fas ligand (Fas-L) system. We provide first time evidence that TRAIL is a potent inducer of apoptosis in multiple myeloma (MM) cell lines. TRAIL effectively induced extensive apoptosis in 8226 and ARP-1 MM cells in a time- and dose-dependent manner. Apoptosis with TRAIL reached about 80% within 48 h of treatment with a dose of 160 ng/ml. Furthermore, we provide first time evidence that similar to Fas, TRAIL-induced apoptosis is not blocked by bcl-2 in MM cell lines. Most importantly, TRAIL induced substantial apoptosis in freshly isolated, flow-sorted myeloma cells obtained from different MM patients expressing variable levels of bcl-2. Finally, we demonstrate for the first time that TRAIL is not cytotoxic to purified CD34+/CD45dim hematopoietic stem cells and does not inhibit CFU-GM or BFU-E colony formation in methylcellulose. |
| Databáze: | OpenAIRE |
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