The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis
| Autor: | S Omura, Jean-Marc Cosset, J Dumont, P Masdehors, Jozo Delic, Henri Magdelenat, J L Binet |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Cancer Research
Proteasome Endopeptidase Complex medicine.medical_treatment Chronic lymphocytic leukemia Lactacystin Apoptosis Biology Cysteine Proteinase Inhibitors Radiation Tolerance chemistry.chemical_compound Multienzyme Complexes medicine Humans Lymphocytes Cytotoxicity Tumor Necrosis Factor-alpha NF-kappa B NFKB1 medicine.disease Leukemia Lymphocytic Chronic B-Cell Acetylcysteine Neoplasm Proteins Cysteine Endopeptidases Cytokine Oncology chemistry Drug Resistance Neoplasm Immunology Cancer research Proteasome inhibitor Tumor necrosis factor alpha medicine.drug Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Apoptosis can be triggered by cytotoxic agents and radiation currently used in cancer treatment. However, the apoptotic response appears to vary between cell types (normal or transformed) and between types of malignancy. Thus, irradiation induces apoptosis in normal human lymphocytes but not in lymphocytes derived from a subset of chronic lymphocytic leukaemia (CLL). Moreover, in this subset, spontaneous apoptosis is inhibited by irradiation. Why irradiation does not allow the initiation of the apoptotic death pathway could be explained, at least in part, and in agreement with recent findings on experimental models, by the activation of the transcriptional factor NF-kappaB, which is able to inhibit apoptotic cell response. Low doses (at which no effect is observed with normal human lymphocytes) of the highly specific proteasome inhibitor lactacystin are sufficient to trigger apoptosis in these malignant cells. Proteasome inhibition by lactacystin prevents the nuclear translocation of both p50 and p65 NF-kappaB subunits and sensitizes these cells to apoptosis by tumour necrosis factor (TNF)-alpha treatment. As this subset of CLL is totally resistant to any treatment, proteasome inhibition by lactacystin provides a new therapeutic approach to be explored, considering the sensitivity of malignant CLL-derived lymphocytes to be quite different from that of normal human lymphocytes. Images Figure 1 Figure 3 |
| Databáze: | OpenAIRE |
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