Tumor Biology

, Volume 36, Issue 2, pp 655–662 | Cite as

Decreasing GSH and increasing ROS in chemosensitivity gliomas with IDH1 mutation

  • Jinlong Shi
  • Baolan Sun
  • Wei Shi
  • Hao Zuo
  • Daming Cui
  • Lanchun Ni
  • Jian Chen
Research Article


Gliomas are the most malignant and aggressive primary brain tumor in adults. Despite concerted efforts to improve therapies, their prognosis remains very poor. Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered frequently in glioma patients and are strongly correlated with improved survival. However, the effect of IDH1 mutations on the chemosensitivity of gliomas remains unclear. In this study, we generated clonal U87 and U251 glioma cell lines overexpressing the R132H mutant protein (IDH1-R132H). Compared with control cells and cells overexpressing IDH wild type (IDH1-WT), both types of IDH1-R132H cells were more sensitive to temozolomide (TMZ) and cis-diamminedichloroplatinum (CDDP) in a time- and dose-dependent manner. The IDH1-R132H-induced higher chemosensitivity was associated with nicotine adenine disphosphonucleotide (NADPH), glutathione (GSH) depletion, and reactive oxygen species (ROS) generation. Accordingly, this IDH1-R132H-induced growth inhibition was effectively abrogated by GSH in vitro and in vivo. Our study provides direct evidence that the improved survival in patients with IDH1-R132H tumors may partly result from the effects of the IDH1-R132H protein on chemosensitivity. The primary cellular events associated with improved survival are the GSH depletion and increased ROS generation.


Gliomas Isocitrate dehydrogenase 1 Glutathione Reactive oxygen species Chemotherapy 



This study was supported by the Youth Fund of the National Natural Science Foundation of China (81201975; 81201979; 81201349), the Youth Fund of the Natural Science Foundation of Jiangsu Province (BK2012224), the Natural Science Foundation of China Ministry of Health (2010-2-025), the Natural Science Foundation of Jiangsu Department of Health (H201124), the Six Major Human Resources Project of Jiangsu Province (2011-WS-065; 2010-WS-038), and the Natural Science Foundation of Jiangsu Colleges and Universities Grant (11KJB320010).

Conflicts of interest


Supplementary material

13277_2014_2644_Fig5_ESM.jpg (43 kb)
Fig. S1

U251-IDH1-R132H cells increased the sensitivity to TMZ and CDDP. Cells were treated with varying doses of TMZ (A), CDDP (B), VCR (C), and VP-16 (D) for different incubation periods. Viability was quantitated with WST-1 assay and expressed as mean percentage of untreated control cells (mean ± SEM, n = 3). *P < 0.05, **P < 0.01 compared with control, IDH1-WT cells. (JPEG 43 kb)

13277_2014_2644_MOESM1_ESM.tif (6.7 mb)
High resolution image (TIFF 6883 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongChina
  2. 2.Department of Neurosurgery, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina

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