Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells.
Acetamides
/ pharmacology
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Ascorbic Acid
/ pharmacology
Benzimidazoles
/ pharmacology
Colonic Neoplasms
/ genetics
DNA Methylation
DNA-Binding Proteins
/ genetics
Dioxygenases
Drug Synergism
Gene Silencing
HCT116 Cells
Humans
Isocitrate Dehydrogenase
/ antagonists & inhibitors
Mixed Function Oxygenases
/ genetics
Mutation
Proto-Oncogene Proteins
/ genetics
IDH1
TET
Vitamin C
cancer cells
epigenetics
Journal
Epigenetics
ISSN: 1559-2308
Titre abrégé: Epigenetics
Pays: United States
ID NLM: 101265293
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
pubmed:
12
9
2019
medline:
22
4
2021
entrez:
12
9
2019
Statut:
ppublish
Résumé
Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite as it inhibits the activity of α-ketoglutarate-dependent dioxygenases such as ten-eleven translocation (TET) enzymes. Inhibitors of mutant IDH enzymes, like ML309, are currently tested in order to lower the levels of 2-HG. Vitamin C (VC) is an inducer of TET enzymes. To test a new therapeutic avenue of synergistic effects, the anti-neoplastic activity of inhibition of mutant IDH1 via ML309 in the presence of VC was investigated in the colon cancer cell line HCT116
Identifiants
pubmed: 31505989
doi: 10.1080/15592294.2019.1666652
pmc: PMC7028341
doi:
Substances chimiques
2-(2-(1H-benzo(d)imidazol-1-yl)-N-(3-fluorophenyl)acetamido)-N-cyclopentyl-2-o-tolylacetamide
0
Acetamides
0
Antineoplastic Agents
0
Benzimidazoles
0
DNA-Binding Proteins
0
Proto-Oncogene Proteins
0
Mixed Function Oxygenases
EC 1.-
TET1 protein, human
EC 1.-
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Dioxygenases
EC 1.13.11.-
TET2 protein, human
EC 1.13.11.-
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
307-322Références
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