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.

Abstract

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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