Nifurtimox induces apoptosis of neuroblastoma cells in vitro and in vivo

Giselle L. Saulnier Sholler, Laurent Brard, Jennifer A. Straub, Lee Dorf, Sharon Illeyne, Karen Koto, Satyan Kalkunte, Marcus Bosenberg, Taka Ashikaga, Rae Nishi

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Neuroblastoma is the most common extracranial solid tumor in children and, when disseminated, carries a poor prognosis. Even with aggressive combinations of chemotherapy, surgery, autologous bone marrow transplant, and radiation, long-term survival remains at 30% and new therapies are needed. Recently, a patient with neuroblastoma who acquired Chagas disease was treated with nifurtimox with subsequent reduction in tumor size. The effect of nifurtimox on the neuroblastoma cell lines CHLA-90, LA1-55n, LA-N2, SMS-KCNR, and SY5Y was examined. Nifurtimox decreased cell viability in a concentration-dependent manner. Cell morphology, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay, and caspase-3 activation indicate that cell death was primarily due to apoptosis. Nifurtimox also suppressed basal and TrkB-mediated Akt phosphorylation, and the cytotoxicity of nifurtimox was attenuated by a tyrosine hydroxylase inhibitor (alpha-methyl-tyrosine). Nifurtimox killed catecholaminergic, but not cholinergic, autonomic neurons in culture. In vivo xenograft models showed inhibition of tumor growth with a histologic decrease in proliferation and increase in apoptosis. These results suggest that nifurtimox induces cell death in neuroblastoma. Therefore, further studies are warranted to develop nifurtimox as a promising new treatment for neuroblastoma.

Original languageEnglish (US)
Pages (from-to)187-193
Number of pages7
JournalJournal of pediatric hematology/oncology
Issue number3
StatePublished - Mar 2009

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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