Bortezomib Induces Apoptosis of Epstein-barr Virus (Ebv)-transformed B Cells and Prolongs Survival of Mice Inoculated with Ebv-transformed B Cells.
From: Laboratory of Clinical Infectious Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Journal of virology
- Publish Date: Sep 2007
- ISSN: 0022-538X
- Volume: 81
- Issue: 18
- Pages: 10029-36
- Medium: Print
- Language: English
- Citation (JAMA): Zou Ping, Kawada Junichi, Pesnicak Lesley, et al. Bortezomib Induces Apoptosis of Epstein-barr Virus (Ebv)-transformed B Cells and Prolongs Survival of Mice Inoculated with Ebv-transformed B Cells.. J. Virol. Sep 2007;81:10029-36
Abstract
Bortezomib, an inhibitor of the 26S proteasome, is currently approved for treatment of multiple myeloma and is being studied for therapy of non-Hodgkin’s lymphoma. We found that Epstein-Barr virus (EBV)-positive B cells with type III latency were more susceptible to killing by bortezomib than those with type I latency. Bortezomib induced apoptosis of EBV lymphoblastoid cell lines (LCLs) by inducing cleavage of caspases 8 and 9; apoptosis was inhibited by pretreatment with a pan-caspase inhibitor. Bortezomib reduced the levels of the p50 and p65 components of the canonical NF-kappaB pathway and reduced the level of p52 in the noncanonical NF-kappaB pathway, which is induced by EBV LMP1. Bortezomib inhibited expression of cIAP-1, cIAP-2, and XIAP, which are regulated by NF-kappaB and function as inhibitors of apoptosis. Bortezomib did not inhibit expression of several other antiapoptotic proteins, including Bcl-2 and Bcl-XL. Finally, bortezomib significantly prolonged the survival of severe combined immunodeficiency mice inoculated with LCLs. These findings suggest that bortezomib may represent a novel strategy for the treatment of certain EBV-associated lymphomas.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Apoptosis, Boronic Acids, Burkitt Lymphoma, Caspase 8, Caspase 9, Cell Line, Tumor, Cell Transformation, Viral, Herpesvirus 4, Human, Humans, Inhibitor of Apoptosis Proteins, Mice, Mice, SCID, Multiple Myeloma, NF-kappa B p50 Subunit, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-bcl-2, Pyrazines, Signal Transduction, Transcription Factor RelA, Viral Matrix Proteins, Virus Latency, X-Linked Inhibitor of Apoptosis Protein, Xenograft Model Antitumor Assays, bcl-X Protein
Check for Full Text / PubMed Unique Identifier (PMID): 17626072
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