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Updated: Nov 11, 2025

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Published on: April 13, 2022
The amino acid metabolism is essential for evading physical plasma-induced tumour cell death
Rajesh Kumar Gandhirajan1, Dorothee Meyer2, Sanjeev Kumar Sagwal2
1ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany. rajesh.gandhirajan@inp-greifswald.de.
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.
Insights
Cancer cells utilize amino acids during cold physical plasma treatment, influencing cell death. Targeting amino acid influx could enhance anti-cancer therapies.
Area of Science:
- Oncology
- Biochemistry
- Plasma Medicine
Background:
- Amino acids play a crucial role in cancer metabolism.
- Cold physical plasma generates reactive oxygen species (ROS) to target tumor cells.
- The impact of metabolic reprogramming on plasma-induced cancer cell death is not well understood.
Purpose of the Study:
- To investigate the utilization and impact of major metabolic substrates (fatty acid, amino acid, TCA pathways) in tumor cells after plasma exposure.
- To understand the role of metabolic reprogramming in modulating cancer cell death induced by cold physical plasma.
Main Methods:
- Utilized quantitative real-time PCR (qPCR) and immunoblotting to analyze gene and protein expression.
- Assessed cell death using cell death analysis assays.
- Investigated metabolic substrate utilization in various tumor cell lines (Panc-1, HeLa, OVCAR3, SK-MEL-28).
Main Results:
- Metabolic substrates were utilized by Panc-1 and HeLa cells but not OVCAR3 and SK-MEL-28 cells post-plasma treatment.
- ASCT2 and SLC3A2 genes were upregulated in multiple cell lines (Panc-1, Miapaca2GR, HeLa, MeWo) after plasma exposure.
- Knockdown of ASCT2, glutamine depletion, or V9302 inhibition sensitized HeLa cells to plasma-induced death; glutamine, valine, or tyrosine supplementation improved cell metabolism and viability.
Conclusions:
- Amino acid influx drives metabolic reprogramming in tumor cells treated with physical plasma, affecting cell death extent.
- Targeting amino acid metabolism pathways in combination with physical plasma could be a potential anti-cancer strategy.
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