Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas

PLoS One. 2013 Nov 8;8(11):e79474. doi: 10.1371/journal.pone.0079474. eCollection 2013.

Abstract

Background: Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans.

Methodology/principal findings: Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice.

Conclusion/significance: These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Arsenic / administration & dosage*
  • Cell Line, Tumor
  • Drug Synergism
  • Herpesvirus 8, Human / drug effects*
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / pathogenicity
  • Humans
  • Interferon-alpha / administration & dosage*
  • Lymphoma, Primary Effusion / drug therapy*
  • Lymphoma, Primary Effusion / pathology
  • Lymphoma, Primary Effusion / virology
  • Mice
  • Transcription, Genetic / drug effects

Substances

  • Interferon-alpha
  • Arsenic

Grants and funding

This project is supported by grants from the Lebanese National Council for Scientific Research (LNCSR), Lebanese University/EDST, and American University of Beirut (Medical Practice Plan and University Research Board). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.