The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance.
RONS
Trx
TrxR
antioxidative defence
oxidative stress
resistance to therapy
Journal
Frontiers in molecular biosciences
ISSN: 2296-889X
Titre abrégé: Front Mol Biosci
Pays: Switzerland
ID NLM: 101653173
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
02
2022
accepted:
22
04
2022
entrez:
6
6
2022
pubmed:
7
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
The intracellular redox homeostasis is a dynamic balancing system between the levels of free radical species and antioxidant enzymes and small molecules at the core of cellular defense mechanisms. The thioredoxin (Trx) system is an important detoxification system regulating the redox milieu. This system is one of the key regulators of cells' proliferative potential as well, through the reduction of key proteins. Increased oxidative stress characterizes highly proliferative, metabolically hyperactive cancer cells, which are forced to mobilize antioxidant enzymes to balance the increase in free radical concentration and prevent irreversible damage and cell death. Components of the Trx system are involved in high-rate proliferation and activation of pro-survival mechanisms in cancer cells, particularly those facing increased oxidative stress. This review addresses the importance of the targetable redox-regulating Trx system in tumor progression, as well as in detoxification and protection of cancer cells from oxidative stress and drug-induced cytotoxicity. It also discusses the cancer cells' counteracting mechanisms to the Trx system inhibition and presents several inhibitors of the Trx system as prospective candidates for cytostatics' adjuvants. This manuscript further emphasizes the importance of developing novel multitarget therapies encompassing the Trx system inhibition to overcome cancer treatment limitations.
Identifiants
pubmed: 35664671
doi: 10.3389/fmolb.2022.883297
pii: 883297
pmc: PMC9161637
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
883297Informations de copyright
Copyright © 2022 Jovanović, Podolski-Renić, Krasavin and Pešić.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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