Pharmacological Strategy for Selective Targeting of Glioblastoma by Redox-active Combination Drug-Comparison With the Chemotherapeutic Standard-of-care Temozolomide

Background/Aim: We describe a pharmacological strategy for selectively targeting glioblastoma using a redoxactive combination drug menadione/ascorbate (M/A), compared to the chemotherapeutic standard-of-care temozolomide (TMZ). Materials and Methods: Experiments were conducted on glioblastoma mice (GS9L cell transplants - intracranial model), treated with M/A or TMZ. Tumor growth was monitored by magnetic resonance imaging. Effects of M/A and TMZ on cell viability and overproduction of mitochondrial superoxide were also evaluated on isolated glioblastoma cells (GS9L) and normal microglial cells (EOC2). Results: M/A treatment suppressed tumor growth and increased survival without adverse drug-related side effects that were characteristic of TMZ. Survival was comparable with that of TMZ at the doses we have tested so far, although the effect of M/A on tumor growth was less pronounced than that of TMZ. M/A induced highly specific cytotoxicity accompanied by dose-dependent overproduction of mitochondrial superoxide in glioblastoma cells, but not in normal microglial cells. Conclusion: M/A differentiates glioblastoma cells from normal microglial cells, causing redox alterations and oxidative stress only in the tumor. This easier-to-tolerate treatment has a potential to support the surgery and conventional therapy of glioblastoma.

Automated summary

The research demonstrates that M/A is a more tolerable pharmacological strategy for selectively targeting glioblastoma, suppressing tumor growth. M/A induces overproduction of mitochondrial superoxide specifically in glioblastoma cells, distinguishing them from normal microglial cells.