Azidothymidine inhibits NF-κB and induces Epstein-Barr virus gene expression in Burkitt lymphoma

Motoki Kurokawa, 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

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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-κB (NF-κB) subunits p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV + BL lines with AZT inhibited NF-κB 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-κB and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
Issue number1
StatePublished - Jul 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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