Cytotoxic and Radiosensitising Effects of a Novel Thioredoxin Reductase Inhibitor in Brain Cancers

• DOI: 10.1007/s12035-022-02808-4
• Publication Date: 2022-03-28T13:05:38Z
• Authors: Anqi Yao; Sarah J. Storr; Martyn Inman; Lucy Barwell; Christopher J. Moody; Stewart G. Martin
• Keywords: Clonogenic assay; Temozolomide

The thioredoxin (Trx) system, a key antioxidant pathway, represents an attractive target for cancer therapy. This study investigated the chemotherapeutic and radiosensitising effects of novel Trx reductase (TrxR) inhibitor, IQ10, on brain cells underlying mechanisms action. Five cell lines normal type were used. TrxR activity expression assessed by insulin reduction assay Western blotting, respectively. IQ10 cytotoxicity was evaluated using growth curve, resazurin clonogenic assays. Radiosensitivity examined assay. Reactive oxygen species levels flow cytometry DNA damage immunofluorescence. Epithelial-mesenchymal transition (EMT)-related gene RT-PCR array. significantly inhibited but did not affect system protein in cells. drug exhibited potent anti-proliferative cytotoxic against under both normoxic hypoxic conditions 2D 3D systems, with IC50s low micromolar range. It up to ~ 1000-fold more than temozolomide. substantially sensitised various radiation, such effect being due, part, functional inhibition TrxR, making less able deal oxidative stress leading increased damage. downregulated EMT-associated suggesting potential anti-invasive antimetastatic properties. suggests that is anticancer agent could be used as either single or combined treat cancers.