The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma.
3-Hydroxybutyric Acid
/ pharmacology
Animals
Blood Glucose
/ analysis
Cell Line, Tumor
Cell Proliferation
/ drug effects
Diet, Ketogenic
Glioma
/ diet therapy
Glucose
/ pharmacology
Humans
Isocitrate Dehydrogenase
/ genetics
Kaplan-Meier Estimate
Mice
Mice, Nude
Mutation
Transplantation, Heterologous
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
06
10
2021
accepted:
17
01
2022
entrez:
8
2
2022
pubmed:
9
2
2022
medline:
3
3
2022
Statut:
epublish
Résumé
Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut) or, less commonly, IDH2 (together called "IDHmut"). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut or IDHwt glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to an unrestricted, cycling form of KD.
Identifiants
pubmed: 35134075
doi: 10.1371/journal.pone.0257725
pii: PONE-D-21-27756
pmc: PMC8824343
doi:
Substances chimiques
Blood Glucose
0
Isocitrate Dehydrogenase
EC 1.1.1.41
Glucose
IY9XDZ35W2
3-Hydroxybutyric Acid
TZP1275679
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
e0257725Subventions
Organisme : NCI NIH HHS
ID : P50 CA221747
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102669
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117104
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118039
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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