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- W4250948075 abstract "Abstract The thioredoxin (Trx) system, a key antioxidant pathway, represents an attractive target for cancer therapy. This study investigated the chemotherapeutic and radiosensitising effects of a novel Trx reductase (TrxR) inhibitor, IQ10, on brain cancer cells and the underlying mechanisms. Five brain cancer cell lines and a normal cell type were used. TrxR activity and expression were assessed by insulin reduction assay and Western blotting respectively. IQ10 cytotoxicity was evaluated using growth curve, resazurin reduction and clonogenic assays. Radiosensitivity was examined using clonogenic assay. Reactive oxygen species levels were examined by flow cytometry and DNA damage assessed by immunofluorescence. Epithelial-mesenchymal transition (EMT) related genes expression was examined by RT-PCR array. IQ10 significantly inhibited TrxR activity but did not affect the Trx system protein expression in brain cancer cells. The drug exhibited potent anti-proliferative and cytotoxic effects against brain cancer cells under both normoxic and hypoxic conditions in both 2D and 3D systems, with IC 50 s in the low micromolar range. It was up to ~1000 fold more potent than temozolomide. IQ10 substantially sensitised various brain cancer cells to radiation, with such effect being due, in part, to functional inhibition of TrxR, making cells less able to deal with oxidative stress, and leading to increased oxidative DNA damage. IQ10 significantly downregulated EMT associated gene expression suggesting potential antiinvasive and antimetastatic properties. This study suggests that IQ10 is a potent anticancer agent, and could be used as either a single agent or combined with radiation, to treat brain cancers." @default.
- W4250948075 created "2022-05-12" @default.
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- W4250948075 date "2021-10-19" @default.
- W4250948075 modified "2023-10-16" @default.
- W4250948075 title "Cytotoxic and Radiosensitising Effects of a Novel Thioredoxin Reductase Inhibitor in Brain Cancers" @default.
- W4250948075 doi "https://doi.org/10.21203/rs.3.rs-987333/v1" @default.
- W4250948075 hasPublicationYear "2021" @default.
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