α-Ketoglutarate supplementation and NAD+ modulation enhance metabolic rewiring and radiosensitization in SLC25A1 inhibited cancer cells.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
15 Jan 2024
15 Jan 2024
Historique:
received:
18
07
2023
accepted:
04
01
2024
revised:
22
12
2023
medline:
16
1
2024
pubmed:
16
1
2024
entrez:
15
1
2024
Statut:
epublish
Résumé
Metabolic rewiring is the result of the increasing demands and proliferation of cancer cells, leading to changes in the biological activities and responses to treatment of cancer cells. The mitochondrial citrate transport protein SLC25A1 is involved in metabolic reprogramming offering a strategy to induce metabolic bottlenecks relevant to radiosensitization through the accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) upon SLC25A1 inhibition (SLC25A1i). Previous studies have revealed the comparative effects of SLC25A1i or cell-permeable D-2HG (octyl-D-2HG) treatments on DNA damage induction and repair, as well as on energy metabolism and cellular function, which are crucial for the long-term survival of irradiated cells. Here, α-ketoglutarate (αKG), the precursor of D-2HG, potentiated the effects observed upon SLC25A1i on DNA damage repair, cell function and long-term survival in vitro and in vivo, rendering NCI-H460 cancer cells more vulnerable to ionizing radiation. However, αKG treatment alone had little effect on these phenotypes. In addition, supplementation with nicotinamide (NAM), a precursor of NAD (including NAD
Identifiants
pubmed: 38225236
doi: 10.1038/s41420-024-01805-x
pii: 10.1038/s41420-024-01805-x
doi:
Types de publication
Journal Article
Langues
eng
Pagination
27Subventions
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 02NUK061B
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : MA 8970/1-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK1739/2
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 860245
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 860245
Informations de copyright
© 2024. The Author(s).
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