Nifurtimox Induces Apoptosis of Neuroblastoma Cells In Vitro and In Vivo.
 

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03-06-09 08:24 AM
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Nifurtimox Induces Apoptosis of Neuroblastoma Cells In Vitro and In Vivo.
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Nifurtimox Induces Apoptosis of Neuroblastoma Cells In Vitro and In Vivo.

J Pediatr Hematol Oncol. 2009 Mar;31(3):187-193

Authors: Saulnier Sholler GL, Brard L, Straub JA, Dorf L, Illeyne S, Koto K, Kalkunte S, Bosenberg M, Ashikaga T, Nishi R

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.

PMID: 19262245 [PubMed - as supplied by publisher]