Diallyl trisulfide sensitizes radiation therapy on glioblastoma through directly targeting thioredoxin 1.
Free Radic Biol Med
; 189: 157-168, 2022 08 20.
Article
em En
| MEDLINE
| ID: mdl-35921994
ABSTRACT
Radiotherapy is a standard-of-care treatment approach for glioblastoma (GBM) patients, but therapeutic resistance to radiotherapy remains a major challenge. Here we demonstrate that diallyl trisulfide (DATS) directly conjugates with cysteine (C) 32 and C35 (C32/35) residues of thioredoxin 1 (Trx1) through Michael addition reactions. Due to localizing in activity center of Trx1, the conjugation between DATS and C32/35 results in inhibition of Trx1 activity, therefore disturbing thioredoxin system and leading to accumulated levels of reactive oxygen species (ROS). High levels of Trx1 expression are correlated with poor prognosis of glioma patients. Notably, we reveal that DATS synergistically enhances irradiation (IR)-induced ROS accumulation, apoptosis, DNA damage, as well as inhibition of tumor growth of GBM cells. These findings highlight the potential benefits of DATS in sensitizing radiotherapy of GBM patients.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Glioblastoma
/
Compostos Alílicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
/
MEDICINA
Ano de publicação:
2022
Tipo de documento:
Article