| Literature DB >> 15790788 |
Motoki Kurokawa1, Subrata K Ghosh, Juan Carlos Ramos, Abdul M Mian, Ngoc L Toomey, Lisa Cabral, Denise Whitby, Glen N Barber, Dirk P Dittmer, William J Harrington.
Abstract
The antiviral compound azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early-passage, Epstein-Barr virus-positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's antitumor activity. The nuclei of these cells contain activated nuclear factor-kappaB (NF-kappaB) subunits p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-kappaB within 1 to 2 hours. This was followed by up-regulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not ganciclovir (GCV) was highly phosphorylated to its monophosphate form (AZT-MP). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-kappaB and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL.Entities:
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Year: 2005 PMID： 15790788 PMCID： PMC1895122 DOI： 10.1182/blood-2004-09-3748
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113