Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007

Rheal A. Towner, David L. Gillespie, Andrea Schwager, Debra G. Saunders, Nataliya Smith, Charity E. Njoku, Richard S. Krysiak, Chelsea Larabee, Henna Iqbal, Robert A. Floyd, David W.A. Bourne, Osama Abdullah, Edward W. Hsu, Randy L. Jensen

Research output: Contribution to journalArticle

Abstract

BackgroundGlioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitrone compound OKN-007, a disulfonyl derivative of α-phenyl-tert- butyl nitrone.MethodsMRI was used to assess tumor volumes in F98 and U87 gliomas, and bioluminescence imaging was used to measure tumor volumes in F98 gliomas encoded with the luciferase gene (F98luc). Immunohistochemistry was used to assess angiogenesis (vascular endothelial growth factor [VEGF] and microvessel density [MVD]), cell differentiation (carbonic anhydrase IX [CA-IX]), hypoxia (hypoxia-inducible factor-1α [HIF-1α]), cell proliferation (glucose transporter 1 [Glut-1] and MIB-1), proliferation index, and apoptosis (cleaved caspase 3) markers in F98 gliomas. VEGF, CA-IX, Glut-1, HIF-1α, and cleaved caspase 3 were assessed in U87 gliomas.ResultsAnimal survival was found to be significantly increased (P <. 001 for F98, P <. 01 for U87) in the group that received OKN-007 treatment compared with the untreated groups. After MRI detection of F98 gliomas, OKN-007, administered orally, was found to decrease tumor growth (P <. 05). U87 glioma volumes were found to significantly decrease (P <. 05) after OKN-007 treatment, compared with untreated animals. OKN-007 administration resulted in significant decreases in tumor hypoxia (HIF-1α [P <. 05] in both F98 and U87), angiogenesis (MVD [P <. 05], but not VEGF, in F98 or U87), and cell proliferation (Glut-1 [P <. 05 in F98, P <. 01 in U87] and MIB-1 [P <. 01] in F98) and caused a significant increase in apoptosis (cleaved caspase 3 [P <. 001 in F98, P <. 05 in U87]), compared with untreated animals.ConclusionsOKN-007 may be considered as a promising therapeutic addition or alternative for the treatment of aggressive human gliomas.

Original languageEnglish (US)
Pages (from-to)330-340
Number of pages11
JournalNeuro-Oncology
Volume15
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • F98 rat glioma model
  • U87 xenografts
  • anti-glioma therapy
  • bioluminescence imaging
  • in vivo
  • magnetic resonance imaging
  • nitrone OKN-007

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007'. Together they form a unique fingerprint.

  • Cite this

    Towner, R. A., Gillespie, D. L., Schwager, A., Saunders, D. G., Smith, N., Njoku, C. E., Krysiak, R. S., Larabee, C., Iqbal, H., Floyd, R. A., Bourne, D. W. A., Abdullah, O., Hsu, E. W., & Jensen, R. L. (2013). Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007. Neuro-Oncology, 15(3), 330-340. https://doi.org/10.1093/neuonc/nos337