TY - JOUR
T1 - The mutant isocitrate dehydrogenase 1 product, 2‑hydroxyglutarate, activates MutT homolog 1 in glioma cells via the augmentation of reactive oxygen species levels
AU - Bhavya, Bharathan
AU - Anand, Chellapan Reghuvaran
AU - Urulangodi, Madhusoodanan
AU - Sreelakshmi, Kalapurakkal
AU - Deepti, Akkihebbal Narasimhaiah
AU - Menon, Girish Ramachandran
AU - Kesavapisharady, Krishnakumar
AU - Easwer, Hariharan Venkat
AU - Gopala, Srinivas
N1 - Funding Information:
The authors would like to thank the Department of Science and Technology, India for providing the INSPIRE Fellowship (IF150784). The authors also acknowledge the Council of Scientific and Industrial Research [09/523(0082)/2014‑EMR‑1], Government of India for granting Research Fellowship.
Funding Information:
The authors would like to thank the Department of Science and Technology, India for providing the INSPIRE Fellowship (IF150784). The authors also acknowledge the Council of ScientificandIndustrialResearch[09/523(0082)/2014‑EMR‑1], Government of India for granting Research Fellowship.
Publisher Copyright:
© 2022 Spandidos Publications. All Rights Reserved.
PY - 2022
Y1 - 2022
N2 - 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) produc‑ tion 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.
AB - 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) produc‑ tion 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.
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U2 - 10.3892/wasj.2022.174
DO - 10.3892/wasj.2022.174
M3 - Article
AN - SCOPUS:85141015921
SN - 2632-2900
VL - 4
JO - World Academy of Sciences Journal
JF - World Academy of Sciences Journal
IS - 6
M1 - 39
ER -
