Treatment of Akata EBV-positive cells with doxorubicin causes more EBV reactivation than treatment with etoposide

Chemotherapy. 2011;57(3):195-203. doi: 10.1159/000323627. Epub 2011 Apr 29.

Abstract

Background/aims: EBV has been associated with Burkitt lymphoma (BL). It establishes a latent infection but its reactivation has been observed in patients receiving long-term chemotherapy. The effect of doxorubicin on virus reactivation has been described previously, but the effect of etoposide or cytarabine on EBV reactivation has not been reported in the literature. The aim of this work was to carry out such a study.

Methods: Akata EBV-positive cell lines were treated with etoposide, doxorubicin or cytarabine. Viable cells were analyzed by trypan blue, programmed cell death by TUNEL assay, mRNA levels by RT-PCR and cellular or viral proteins by Western blot. Viruses were visualized by electron microscopy.

Results: All of the studied drugs caused cell death by apoptosis. Comparing the effect of etoposide and doxorubicin (at their IC(50)) in the EBV-positive cells, etoposide caused less EBV reactivation than doxorubicin. Cytarabine apparently did not reactivate EBV.

Conclusion: When treating Akata EBV-positive cells with the respective IC(50) of the following drugs, etoposide induced less EBV reactivation than doxorubicin, and cytarabine apparently did not induce EBV reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Etoposide / pharmacology*
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / genetics
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Viral / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Antineoplastic Agents
  • BZLF1 protein, Herpesvirus 4, Human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Viral
  • Trans-Activators
  • Etoposide
  • Doxorubicin