The mutant isocitrate dehydrogenase 1 product, 2‑hydroxyglutarate, activates MutT homolog 1 in glioma cells via the augmentation of reactive oxygen species levels

Abstract

MutT homolog1 (MTH1) is an enzyme responsible for removing oxidized nucleotides from cells. The activation of MTH1 has been reported in a number of cancer cell types and is considered to be responsible for imparting resistance towards anticancer drugs. While there are several known mechanisms for the activation of MTH1 in cancer cells, the present study aimed to evaluate the role of mutant isocitrate dehydrogenase1 (mIDH1)-mediated reactive oxygen species (ROS) production in the activation of MTH1 in glioma cells. MTH1 was found to be upregulated in both mIDH1-expressing cells and 2-hydroxyglutarate (2-HG)-treated cells. mIDH1 and its product, 2-HG, increased the levels of ROS in cultured glioblastoma cells. Furthermore, the increased expression and activity of MTH1 were observed in glioma tissues harboring mIDH1 compared to tissues with wild-type IDH1. On the whole, the findings of the present study unveil a novel mechanism of activation of MTH1 in glioma cells harboring mutant IDH1.