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.