Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells.
AMPK
HCC
TCA cycle
growth
metabolomics
migration
proteomics
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
16 11 2020
16 11 2020
Historique:
received:
29
07
2020
revised:
05
11
2020
accepted:
12
11
2020
entrez:
19
11
2020
pubmed:
20
11
2020
medline:
1
7
2021
Statut:
epublish
Résumé
Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.
Identifiants
pubmed: 33207837
pii: cells9112491
doi: 10.3390/cells9112491
pmc: PMC7696226
pii:
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Methionine
AE28F7PNPL
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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