An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth and infiltration of EBV-positive lymphoblastoid B cells
| Autor: | Harutaka Katano, Mariko Tomita, Michiko Yamamoto, Naoki Yamamoto, Md. Zahidunnabi Dewan, Tetsutaro Sata, Norio Yamamoto, Naoki Mori, Sunjida Ahmed |
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| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
Epstein-Barr Virus Infections Herpesvirus 4 Human Cancer Research Lymphoma B-Cell Blotting Western Apoptosis Electrophoretic Mobility Shift Assay Biology medicine.disease_cause Polymerase Chain Reaction Virus Mice Cyclin D2 Cell Movement hemic and lymphatic diseases Survivin medicine Animals Humans HIV Protease Inhibitor In Situ Hybridization Fluorescence Cell Proliferation Ritonavir Lymphoblast Cell Cycle NF-kappa B HIV Protease Inhibitors medicine.disease Xenograft Model Antitumor Assays Virology Epstein–Barr virus Lymphoma Oncology medicine.drug |
| Zdroj: | International Journal of Cancer. 124:622-629 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Epstein-Barr Virus (EBV)-associated immunoblastic lymphoma occurs in immunocompromised patients such as those with AIDS or transplant recipients after primary EBV infection or reactivation of a preexisting latent EBV infection. In the present study, we evaluated the effect of ritonavir, an HIV protease inhibitor, on EBV-positive lymphoblastoid B cells in vitro and in mice model. We found that it induced cell-cycle arrest at G1-phase and apoptosis through down-regulation of cell-cycle gene cyclin D2 and antiapoptotic gene survivin. Furthermore, ritonavir suppressed transcriptional activation of NF-κB in these cells. Ritonavir efficiently prevented growth and infiltration of lymphoma cells in various organs of NOD/SCID/γcnull mice at the same dose used for treatment of patients with AIDS. Our results indicate that ritonavir targets NF-κB activated in tumor cells and shows anti-tumor effects. These data also suggest that this compound may have promise for treatment or prevention of EBV-associated lymphoproliferative diseases that occur in immunocompromised patients. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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