OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.
8-oxoG
Base Excision Repair (BER)
OGG1
OGG1 inhibitor
SU0268
TH5487
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2023
2023
Historique:
received:
15
12
2022
accepted:
17
01
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
24
2
2023
Statut:
epublish
Résumé
One of the most abundant DNA lesions induced by Reactive oxygen species (ROS) is 8-oxoG, a highly mutagenic lesion that compromises genetic instability when not efficiently repaired. 8-oxoG is specifically recognized by the DNA-glycosylase OGG1 that excises the base and initiates the Base Excision Repair pathway (BER). Furthermore, OGG1 has not only a major role in DNA repair but it is also involved in transcriptional regulation. Cancer cells are particularly exposed to ROS, thus challenging their capacity to process oxidative DNA damage has been proposed as a promising therapeutic strategy for cancer treatment. Two competitive inhibitors of OGG1 (OGG1i) have been identified, TH5487 and SU0268, which bind to the OGG1 catalytic pocket preventing its fixation to the DNA. Early studies with these inhibitors show an enhanced cellular sensitivity to cytotoxic drugs and a reduction in the inflammatory response. Our study uncovers two unreported off-targets effects of these OGG1i that are independent of OGG1.
Identifiants
pubmed: 36819096
doi: 10.3389/fcell.2023.1124960
pii: 1124960
pmc: PMC9936318
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1124960Informations de copyright
Copyright © 2023 Tanushi, Pinna, Vandamme, Siberchicot, D’Augustin, Di Guilmi, Radicella, Castaing, Smith, Huet, Leteurtre and Campalans.
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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