| Autor: |
Sophie A. Twigger, Blanca Dominguez, Vanesa Porto, Lina Hacker, Anthony J. Chalmers, Ross Breckenridge, Martin Treder, Adam C. Sedgwick, Fernando Dominguez, Ester M. Hammond |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 76, Iss , Pp 103326- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2024.103326 |
| Popis: |
Regions of hypoxia occur in most solid tumours and are known to significantly impact therapy response and patient prognosis. Ag5 is a recently reported silver molecular cluster which inhibits both glutathione and thioredoxin signalling therefore limiting cellular antioxidant capacity. Ag5 treatment significantly reduces cell viability in a range of cancer cell lines with little to no impact on non-transformed cells. Characterisation of redox homeostasis in hypoxia demonstrated an increase in reactive oxygen species and glutathione albeit with different kinetics. Significant Ag5-mediated loss of viability was observed in a range of hypoxic conditions which mimic the tumour microenvironment however, this effect was reduced compared to normoxic conditions. Reduced sensitivity to Ag5 in hypoxia was attributed to HIF-1 mediated signalling to reduce PDH via PDK1/3 activity and changes in mitochondrial oxygen availability. Importantly, the addition of Ag5 significantly increased radiation-induced cell death in hypoxic conditions associated with radioresistance. Together, these data demonstrate Ag5 is a potent and cancer specific agent which could be used effectively in combination with radiotherapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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