The amino acid metabolism is essential for evading physical plasma-induced tumour cell death.
Amino Acids
/ metabolism
Argon
/ pharmacology
Cell Death
/ drug effects
Cells, Cultured
Drug Resistance, Neoplasm
/ physiology
Energy Metabolism
/ physiology
Gene Expression Regulation, Neoplastic
/ drug effects
HeLa Cells
Humans
Metabolic Networks and Pathways
/ drug effects
Metabolome
/ drug effects
Neoplasms
/ genetics
Plasma Gases
/ pharmacology
Reactive Oxygen Species
/ metabolism
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
16
10
2020
accepted:
26
02
2021
revised:
10
02
2021
pubmed:
27
3
2021
medline:
16
12
2021
entrez:
26
3
2021
Statut:
ppublish
Résumé
Recent studies have emphasised the important role of amino acids in cancer metabolism. Cold physical plasma is an evolving technology employed to target tumour cells by introducing reactive oxygen species (ROS). However, limited understanding is available on the role of metabolic reprogramming in tumour cells fostering or reducing plasma-induced cancer cell death. The utilisation and impact of major metabolic substrates of fatty acid, amino acid and TCA pathways were investigated in several tumour cell lines following plasma exposure by qPCR, immunoblotting and cell death analysis. Metabolic substrates were utilised in Panc-1 and HeLa but not in OVCAR3 and SK-MEL-28 cells following plasma treatment. Among the key genes governing these pathways, ASCT2 and SLC3A2 were consistently upregulated in Panc-1, Miapaca2GR, HeLa and MeWo cells. siRNA-mediated knockdown of ASCT2, glutamine depletion and pharmacological inhibition with V9302 sensitised HeLa cells to the plasma-induced cell death. Exogenous supplementation of glutamine, valine or tyrosine led to improved metabolism and viability of tumour cells following plasma treatment. These data suggest the amino acid influx driving metabolic reprogramming in tumour cells exposed to physical plasma, governing the extent of cell death. This pathway could be targeted in combination with existing anti-tumour agents.
Sections du résumé
BACKGROUND
Recent studies have emphasised the important role of amino acids in cancer metabolism. Cold physical plasma is an evolving technology employed to target tumour cells by introducing reactive oxygen species (ROS). However, limited understanding is available on the role of metabolic reprogramming in tumour cells fostering or reducing plasma-induced cancer cell death.
METHODS
The utilisation and impact of major metabolic substrates of fatty acid, amino acid and TCA pathways were investigated in several tumour cell lines following plasma exposure by qPCR, immunoblotting and cell death analysis.
RESULTS
Metabolic substrates were utilised in Panc-1 and HeLa but not in OVCAR3 and SK-MEL-28 cells following plasma treatment. Among the key genes governing these pathways, ASCT2 and SLC3A2 were consistently upregulated in Panc-1, Miapaca2GR, HeLa and MeWo cells. siRNA-mediated knockdown of ASCT2, glutamine depletion and pharmacological inhibition with V9302 sensitised HeLa cells to the plasma-induced cell death. Exogenous supplementation of glutamine, valine or tyrosine led to improved metabolism and viability of tumour cells following plasma treatment.
CONCLUSION
These data suggest the amino acid influx driving metabolic reprogramming in tumour cells exposed to physical plasma, governing the extent of cell death. This pathway could be targeted in combination with existing anti-tumour agents.
Identifiants
pubmed: 33767419
doi: 10.1038/s41416-021-01335-8
pii: 10.1038/s41416-021-01335-8
pmc: PMC8144554
doi:
Substances chimiques
Amino Acids
0
Plasma Gases
0
Reactive Oxygen Species
0
Argon
67XQY1V3KH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1854-1863Références
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