Abstract:
: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.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Matés JM,Campos-Sandoval JA,de Los Santos-Jiménez J,Márquez Jdoi
10.1007/s00204-020-02838-8subject
Has Abstractpub_date
2020-08-01 00:00:00pages
2603-2623issue
8eissn
0340-5761issn
1432-0738pii
10.1007/s00204-020-02838-8journal_volume
94pub_type
杂志文章,评审abstract::Several structurally different metal chelating agents were screened for their relative efficacy in counteracting acute manganese intoxication in mice. Polyaminocarboxylic acids with nitrogen and oxygen as metal binding sites were more effective than certain sulfhydryl chelating agents and common drugs in preventing mo...
journal_title:Archives of toxicology
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abstract::The consumption of plants containing the diterpenoid atractyloside (ATR) causes selective proximal tubule injury, renal failure and death in humans. We have compared the effects of ATR in freshly isolated renal proximal tubules and glomeruli from rat and also in cell lines: NRK, derived from the proximal tubules, and ...
journal_title:Archives of toxicology
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journal_title:Archives of toxicology
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pub_type: 杂志文章
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journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00293567
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pub_type: 杂志文章
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abstract:: ...
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pub_type: 评论,信件
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journal_title:Archives of toxicology
pub_type: 杂志文章
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abstract::Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a poten...
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journal_title:Archives of toxicology
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journal_title:Archives of toxicology
pub_type: 杂志文章
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journal_title:Archives of toxicology
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pub_type: 杂志文章
doi:10.1007/s00204-005-0660-x
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