RT Journal Article
T1 Glutaminases regulate glutathione and oxidative stress in cancer.
A1 Mates-Sánchez, José Manuel
A1 Campos-Sandoval, José Ángel
A1 De los Santos-Jiménez, Juan
A1 Márquez-Gómez, Javier
K1 Cáncer - Aspectos moleculares
K1 Estrés oxidativo
AB Targeted therapies against cancer have improved both survival and quality of life of patients. However, metabolic rewiring evokes cellular mechanisms that reduce therapeutic mightiness. Resistant cells generate more glutathione, elicit nuclear factor erythroid 2-related factor 2 (NRF2) activation, and overexpress many anti-oxidative genes such as superoxide dismutase, catalase, glutathione peroxidase, and thioredoxin reductase, providing stronger antioxidant capacity to survive in a more oxidative environment due to the sharp rise in oxidative metabolism and reactive oxygen species generation. These changes dramatically alter tumour microenvironment and cellular metabolism itself. A rational design of therapeutic combination strategies is needed to flatten cellular homeostasis and accomplish a drop in cancer development. Context-dependent glutaminase isoenzymes show oncogenic and tumour suppressor properties, being mainly associated to MYC and p53, respectively. Glutaminases catalyze glutaminolysis in mitochondria, regulating oxidative phosphorylation, redox status and cell metabolism for tumour growth. In addition, the substrate and product of glutaminase reaction, glutamine and glutamate, respectively, can work as signalling molecules moderating redox and bioenergetic pathways in cancer. Novel synergistic approaches combining glutaminase inhibition and redox-dependent modulation are described in this review. Pharmacological or genetic glutaminase regulation along with oxidative chemotherapy can help to improve the design of combination strategies that escalate the rate of therapeutic success in cancer patients.
PB Springer Nature
YR 2020
FD 2020
LK https://hdl.handle.net/10630/36790
UL https://hdl.handle.net/10630/36790
LA eng
NO Glutaminases regulate glutathione and oxidative stress in cancer. Matés JM, Campos-Sandoval JA, de Los Santos-Jiménez J, Márquez J. Arch Toxicol. 2020 Aug;94(8):2603-2623. doi: 10.1007/s00204-020-02838-8. Epub 2020 Jul 18. PMID: 32681190
NO https://openpolicyfinder.jisc.ac.uk/id/publication/7855
NO RTI2018-096866-B-I00
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026