PMID- 32681190
OWN - NLM
STAT- MEDLINE
DCOM- 20210712
LR  - 20210712
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 94
IP  - 8
DP  - 2020 Aug
TI  - Glutaminases regulate glutathione and oxidative stress in cancer.
PG  - 2603-2623
LID - 10.1007/s00204-020-02838-8 [doi]
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.
FAU - Mates, Jose M
AU  - Mates JM
AUID- ORCID: 0000-0001-9795-1993
AD  - Department of Molecular Biology and Biochemistry, Canceromics Lab, Faculty of 
      Sciences, University of Malaga, Campus de Teatinos, 29071, Malaga, Spain. 
      jmates@uma.es.
AD  - Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. 
      jmates@uma.es.
FAU - Campos-Sandoval, Jose A
AU  - Campos-Sandoval JA
AD  - Department of Molecular Biology and Biochemistry, Canceromics Lab, Faculty of 
      Sciences, University of Malaga, Campus de Teatinos, 29071, Malaga, Spain.
AD  - Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain.
FAU - de Los Santos-Jimenez, Juan
AU  - de Los Santos-Jimenez J
AD  - Department of Molecular Biology and Biochemistry, Canceromics Lab, Faculty of 
      Sciences, University of Malaga, Campus de Teatinos, 29071, Malaga, Spain.
AD  - Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain.
FAU - Marquez, Javier
AU  - Marquez J
AD  - Department of Molecular Biology and Biochemistry, Canceromics Lab, Faculty of 
      Sciences, University of Malaga, Campus de Teatinos, 29071, Malaga, Spain.
AD  - Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200718
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0RH81L854J (Glutamine)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 3.5.1.2 (GLS protein, human)
RN  - EC 3.5.1.2 (Glutaminase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/therapeutic use
MH  - Antioxidants/therapeutic use
MH  - Energy Metabolism
MH  - Enzyme Inhibitors/therapeutic use
MH  - Glutamic Acid/*metabolism
MH  - Glutaminase/*metabolism
MH  - Glutamine/antagonists & inhibitors/*metabolism
MH  - Glutathione/*metabolism
MH  - Humans
MH  - Mitochondria/drug effects/enzymology/pathology
MH  - Neoplasms/drug therapy/*enzymology/pathology
MH  - *Oxidative Stress/drug effects
MH  - Signal Transduction
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - GLS
OT  - GLS2
OT  - MYC
OT  - NRF2
OT  - Reactive oxygen species
OT  - p53
EDAT- 2020/07/19 06:00
MHDA- 2021/07/13 06:00
CRDT- 2020/07/19 06:00
PHST- 2020/07/02 00:00 [received]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/07/19 06:00 [pubmed]
PHST- 2021/07/13 06:00 [medline]
PHST- 2020/07/19 06:00 [entrez]
AID - 10.1007/s00204-020-02838-8 [pii]
AID - 10.1007/s00204-020-02838-8 [doi]
PST - ppublish
SO  - Arch Toxicol. 2020 Aug;94(8):2603-2623. doi: 10.1007/s00204-020-02838-8. Epub 
      2020 Jul 18.