Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas

Richard K Lee, J. P Jian Ping Cai, Vadim Deyev, Parkash S. Gill, Lisa Cabral, Charles Wood, Ram P. Agarwal, Wenle Xia, Lawrence H. Boise, Eckhard Podack, William J. Harrington

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Abstract

Lymphoproliferative diseases that occur in immunocompromised patients are frequently associated with herpesviruses. These patients often fare poorly after treatment with conventional chemotherapy. We reported previously that patients with AIDS-related Burkitt's lymphoma (BL) responded to parenteral azidothymidine (AZT) and IFN-α. We found that EBV-positive lymphoma cells derived from these patients cultured with AZT express CD95 and undergo apoptosis. AZT-mediated apoptosis was caspase dependent and occurred despite Fas receptor blockade. In contrast, EBV-negative lymphomas were resistant to AZT-induced apoptosis, as were EBV-positive lymphomas that expressed high levels of bcl-2. Primary effusion lymphoma (PEL) cell lines infected with human herpesvirus type 8 required IFN-α to potentiate AZT- induced apoptosis. IFN-α did not up-regulate CD95 in BL or PEL but did induce expression of the death receptor ligand, CD95 ligand. AZT-sensitive lymphomas also accumulated significantly higher intracellular AZT monophosphate than did resistant lymphomas. Our data demonstrated distinct apoptotic responses to AZT and IFN-α in herpesvirus-associated lymphomas. EBV-positive BL cells that expressed low BCL-2 levels were sensitive to AZT alone; PEL cells required the addition of IFN-α to enhance apoptosis, and EBV-negative lymphomas were insensitive to both agents. AZT-sensitive BL cells transfected with BCL-2 became resistant. Susceptibility to antivirus- mediated apoptosis may be exploited to improve the therapy of certain herpesvirus-associated lymphomas.

Original languageEnglish
Pages (from-to)5514-5520
Number of pages7
JournalCancer Research
Volume59
Issue number21
StatePublished - Nov 1 1999

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Zidovudine
Herpesviridae
Interferons
Lymphoma
Apoptosis
Human Herpesvirus 4
Burkitt Lymphoma
Primary Effusion Lymphoma
AIDS-Related Lymphoma
CD95 Antigens
Human Herpesvirus 8
Death Domain Receptors
Fas Ligand Protein
Immunocompromised Host
Caspases
Up-Regulation
Ligands
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lee, R. K., Cai, J. P. J. P., Deyev, V., Gill, P. S., Cabral, L., Wood, C., ... Harrington, W. J. (1999). Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas. Cancer Research, 59(21), 5514-5520.

Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas. / Lee, Richard K; Cai, J. P Jian Ping; Deyev, Vadim; Gill, Parkash S.; Cabral, Lisa; Wood, Charles; Agarwal, Ram P.; Xia, Wenle; Boise, Lawrence H.; Podack, Eckhard; Harrington, William J.

In: Cancer Research, Vol. 59, No. 21, 01.11.1999, p. 5514-5520.

Research output: Contribution to journalArticle

Lee, RK, Cai, JPJP, Deyev, V, Gill, PS, Cabral, L, Wood, C, Agarwal, RP, Xia, W, Boise, LH, Podack, E & Harrington, WJ 1999, 'Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas', Cancer Research, vol. 59, no. 21, pp. 5514-5520.
Lee RK, Cai JPJP, Deyev V, Gill PS, Cabral L, Wood C et al. Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas. Cancer Research. 1999 Nov 1;59(21):5514-5520.
Lee, Richard K ; Cai, J. P Jian Ping ; Deyev, Vadim ; Gill, Parkash S. ; Cabral, Lisa ; Wood, Charles ; Agarwal, Ram P. ; Xia, Wenle ; Boise, Lawrence H. ; Podack, Eckhard ; Harrington, William J. / Azidothymidine and interferon-α induce apoptosis in herpesvirus- associated lymphomas. In: Cancer Research. 1999 ; Vol. 59, No. 21. pp. 5514-5520.
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