Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors

Joshua Casaos, Sakibul Huq, Tarik Lott, Raphael Felder, John Choi, Noah Gorelick, Michael Peters, Yuanxuan Xia, Russell Maxwell, Tianna Zhao, Chenchen Ji, Thomas Simon, Julie Sesen, Sarah J. Scotland, Richard E. Kast, Jeffrey Rubens, Eric Raabe, Charles G Eberhart, Eric Jackson, Henry BremBetty Mae Tyler, Nicolas Skuli

Research output: Contribution to journalArticle

Abstract

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive, malignant tumors and are the most common malignant brain tumor in children under 6 months of age. Currently, there is no standard treatment for AT/RT. Recent studies have reported potential anti-tumoral properties of ribavirin, a guanosine analog and anti-viral molecule approved by the Food and Drug Administration for treatment of hepatitis C. We previously demonstrated that ribavirin inhibited glioma cell growth in vitro and in vivo. Based on these results and the fact that no pre-clinical model of ribavirin in AT/RT exists, we decided to investigate the effect of ribavirin on several human AT/RT cell lines (BT12, BT16, and BT37) both in vitro and in vivo. We provide evidence that ribavirin has a significant impact on AT/RT cell growth and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E and/or EZH2 pathways. Interestingly, using scratch wound and transwell Boyden chamber assays, we observed that ribavirin also impairs AT/RT cell migration, invasion, and adhesion. Finally, we demonstrate that ribavirin significantly improves the survival of mice orthotopically implanted with BT12 cells. Our work establishes that ribavirin is effective against AT/RT by decreasing tumoral cell growth and dissemination and could represent a new therapeutic option for children with this deadly disease.

Original languageEnglish (US)
Pages (from-to)8054-8067
Number of pages14
JournalOncotarget
Volume9
Issue number8
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Atypical teratoid/rhabdoid tumor
  • Brain tumors
  • Glioma
  • Ribavirin
  • Therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Casaos, J., Huq, S., Lott, T., Felder, R., Choi, J., Gorelick, N., ... Skuli, N. (2018). Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors. Oncotarget, 9(8), 8054-8067. https://doi.org/10.18632/oncotarget.23883