Azidothymidine and interferon-alpha induce apoptosis in herpesvirus-associated lymphomas
| Autor: | R K, Lee, J P, Cai, V, Deyev, P S, Gill, L, Cabral, C, Wood, R P, Agarwal, W, Xia, L H, Boise, E, Podack, W J, Harrington |
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| Rok vydání: | 1999 |
| Předmět: |
Herpesvirus 4
Human Time Factors Dose-Response Relationship Drug Lymphoma Lymphoma Non-Hodgkin Interferon-alpha Apoptosis Flow Cytometry Transfection Burkitt Lymphoma Up-Regulation Proto-Oncogene Proteins c-bcl-2 Caspases Herpesvirus 8 Human Tumor Cells Cultured Humans fas Receptor Phosphorylation Zidovudine Lymphoma AIDS-Related |
| Zdroj: | Cancer research. 59(21) |
| ISSN: | 0008-5472 |
| Popis: | Lymphoproliferative diseases that occur in immunocompromised patients are frequently associated with herpesviruses. These patients often fare poorly after treatment with conventional chemotherapy. We reported previously that patients with AIDS-related Burkitt's lymphoma (BL) responded to parenteral azidothymidine (AZT) and IFN-alpha. We found that EBV-positive lymphoma cells derived from these patients cultured with AZT express CD95 and undergo apoptosis. AZT-mediated apoptosis was caspase dependent and occurred despite Fas receptor blockade. In contrast, EBV-negative lymphomas were resistant to AZT-induced apoptosis, as were EBV-positive lymphomas that expressed high levels of bcl-2. Primary effusion lymphoma (PEL) cell lines infected with human herpesvirus type 8 required IFN-alpha to potentiate AZT-induced apoptosis. IFN-alpha did not up-regulate CD95 in BL or PEL but did induce expression of the death receptor ligand, CD95 ligand. AZT-sensitive lymphomas also accumulated significantly higher intracellular AZT monophosphate than did resistant lymphomas. Our data demonstrated distinct apoptotic responses to AZT and IFN-alpha in herpesvirus-associated lymphomas. EBV-positive BL cells that expressed low BCL-2 levels were sensitive to AZT alone; PEL cells required the addition of IFN-alpha to enhance apoptosis, and EBV-negative lymphomas were insensitive to both agents. AZT-sensitive BL cells transfected with BCL-2 became resistant. Susceptibility to antivirus-mediated apoptosis may be exploited to improve the therapy of certain herpesvirus-associated lymphomas. |
| Databáze: | OpenAIRE |
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