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

Abstract

OKN-007 may be considered as a promising therapeutic addition or alternative for the treatment of aggressive human gliomas.

OKN-007 decreases free radical levels in a preclinical F98 rat glioma model

“…Our data also suggest that the inhibition of the tumor growth by OKN-007 in different preclinical glioma models, as we have reported previously [8–10], may in part be due to the reduction of free radicals, as demonstrated in this study on F98 gliomas. IHC assessment of commonly studied tumor markers for cell proliferation or differentiation, hypoxia, angiogenesis, and apoptosis indicated that OKN-007 was able to significantly decrease cell proliferation (glucose transporter 1 (Glut-1) and the cell proliferation marker, MIB-1) but not cell differentiation (carbonate anhydrase IX), decrease angiogenesis (microvessel density (MVD; measured as levels of the endothelial marker, CD-31), but not the VEGF), decrease HIF-1α, and increase apoptosis (cleaved caspase 3) compared with untreated controls [8]. OKN-007-induced decreases in Glut-1 and HIF-1α levels seemed to be similar in both F98 and U87 glioma models, whereas increased apoptosis seemed to be more elevated in the F98 gliomas compared to the U87 tumors [8].…”

“…OKN-007 is a small molecule that can traverse the blood–brain barrier, and has anti-inflammatory, antioxidant, and proapoptotic properties [11–36]. Our group has also established that OKN-007 is an effective anticancer agent in rodent preclinical glioma models [8–10], and it is currently undergoing clinical trial assessment as a new investigational drug for recurrent adult glioblastomas.…”

“…OKN-007 (2,4-disulfophenyl-PBN; or disodium 4-[( tert -butylimino) methyl] benzene-1,3-disulfonate N -oxide or disufenton; also previously known as NXY-059) is an anticancer drug [8–10] and free radical spin-trapping agent that inhibits upregulation of inducible nitric oxide synthase (iNOS), decreases glutamate excitotoxicity [11], and has exhibited efficacy as a neuroprotectant. Scientific advancements in our understanding and detection of free radicals in biological systems and their importance in carcinogenesis, as well as the introduction of novel therapeutics such as OKN-007 that act by influencing radicals [8] have dramatically enhanced our ability to assess the role of free radicals in both disease and normal physiology.…”

“…Scientific advancements in our understanding and detection of free radicals in biological systems and their importance in carcinogenesis, as well as the introduction of novel therapeutics such as OKN-007 that act by influencing radicals [8] have dramatically enhanced our ability to assess the role of free radicals in both disease and normal physiology. In this study, we combined mMRI with a Gd–DTPA–albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone macromolecule adducts (anti-DMPO probe), to detect in vivo free radical levels in untreated and OKN-007-treated adult F98 rat glioma models.…”

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

“…Second, the tumoral central core could have had areas of necrosis with hypoxia which would cause decreased expression of luciferase. 39 The imaging information of in vivo BLI in Fischer344/F98 luc model is in good compliance with a previous report in the literature. 40 In short, the well-established Fischer344/F98 luc model can provide convenient, rapid, and non-invasive monitoring of the orthotopic tumor growth.…”