pubmed.ncbi.nlm.nih.gov

An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation - PubMed

An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation

Jinlong Shi et al. Neurol Sci. 2014 Jun.

Abstract

The isocitrate dehydrogenase 1 (IDH1) gene mutation occurs frequently in glioma. While some studies have demonstrated that IDH1 mutations are associated with prolonged survival, the mechanism remains unclear. In this study, we found that growth was significantly inhibited in glioma cells overexpressing the mutated IDH1 gene. Furthermore, these cells were characterized by decreased intracellular NADPH levels accompanied by glutathione (GSH) depletion and reactive oxygen species (ROS) generation. Moreover, the increased apoptosis and the decreased proliferation were found in the glioma cells overexpressing the mutant IDH1 gene. Accordingly, our study demonstrates that using H2O2-regulated mutant IDH1 glioma cells could obviously increase the inhibition of cell growth; nevertheless, GSH had the opposite result. Our study provides direct evidence that mutation of IDH1 profoundly inhibits the growth of glioma cells, and we speculate that this is the major factor behind its association with prolonged survival in glioma. Finally, our study indicates that depletion of GSH and generation of ROS are the primary cellular events associated with this mutation.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Science. 2008 Sep 26;321(5897):1807-12 - PubMed
    1. J Pharmacol Exp Ther. 2011 Jan;336(1):206-14 - PubMed
    1. Nature. 2010 Jun 17;465(7300):966 - PubMed
    1. N Engl J Med. 2008 Jul 31;359(5):492-507 - PubMed
    1. Neuro Oncol. 2009 Aug;11(4):341-7 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources