Dehydroascorbic acid sensitizes cancer cells to system x
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 09 2023
27 09 2023
Historique:
received:
27
02
2023
accepted:
13
09
2023
revised:
07
09
2023
medline:
4
10
2023
pubmed:
27
9
2023
entrez:
26
9
2023
Statut:
epublish
Résumé
Since the discovery of ferroptosis, it has been postulated that this type of cell death could be utilized in treatments for cancer. Unfortunately, several highly aggressive tumor models are resistant to the pharmacological induction of ferroptosis. However, with the use of combined therapies, it is possible to recover sensitivity to ferroptosis in certain cellular models. Here, we discovered that co-treatment with the metabolically stable ferroptosis inducer imidazole ketone erastin (IKE) and the oxidized form of vitamin C, dehydroascorbic acid (DHAA), is a powerful therapy that induces ferroptosis in tumor cells previously resistant to IKE-induced ferroptosis. We determined that DHAA and IKE + DHAA delocalize and deplete GPX4 in tumor cells, specifically inducing lipid droplet peroxidation, which leads to ferroptosis. Moreover, in vivo, IKE + DHAA has high efficacy with regard to the eradication of highly aggressive tumors such as glioblastomas. Thus, the use of IKE + DHAA could be an effective and safe therapy for the eradication of difficult-to-treat cancers.
Identifiants
pubmed: 37752118
doi: 10.1038/s41419-023-06153-9
pii: 10.1038/s41419-023-06153-9
pmc: PMC10522586
doi:
Substances chimiques
Dehydroascorbic Acid
Y2Z3ZTP9UM
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
637Subventions
Organisme : NCI NIH HHS
ID : R35 CA209896
Pays : United States
Informations de copyright
© 2023. The Author(s).
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