Pharmacological Strategy for Selective Targeting of Glioblastoma by Redox-active Combination Drug - Comparison With the Chemotherapeutic Standard-of-care Temozolomide.
Anticancer Res
; 41(12): 6067-6076, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34848461
ABSTRACT
BACKGROUND/AIM:
We describe a pharmacological strategy for selectively targeting glioblastoma using a redox-active combination drug menadione/ascorbate (M/A), compared to the chemotherapeutic standard-of-care temozolomide (TMZ). MATERIALS ANDMETHODS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Glioblastoma
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Antineoplásicos Alquilantes
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Padrão de Cuidado
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Temozolomida
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article