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| Content Provider | Springer Nature Link |
|---|---|
| Author | Shi, Jinlong Sun, Baolan Shi, Wei Zuo, Hao Cui, Daming Ni, Lanchun Chen, Jian |
| Copyright Year | 2014 |
| Abstract | 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. |
| Starting Page | 655 |
| Ending Page | 662 |
| Page Count | 8 |
| File Format | |
| ISSN | 10104283 |
| Journal | Tumor Biology |
| Volume Number | 36 |
| Issue Number | 2 |
| e-ISSN | 14230380 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2014-10-05 |
| Publisher Place | Dordrecht |
| Access Restriction | Subscribed |
| Subject Keyword | Gliomas Isocitrate dehydrogenase 1 Glutathione Reactive oxygen species Chemotherapy Cancer Research |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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