Terahertz radiation alters metabolism and signaling in melanoma cells

Background and objectives

Terahertz (THz) radiation is increasingly explored for biomedical applications, however, its non-thermal effects on cellular metabolism and regulatory networks remain insufficiently characterized. This study aimed to investigate how 2.3 THz radiation affects metabolic pathways and membrane-associated signaling in human melanoma cells.

Methods

SK-MEL-28 melanoma cells were exposed to 2.3 THz radiation for 45 min using the 1st Novosibirsk free-electron laser. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Metabolic alterations were detected by targeted metabolomics using liquid chromatography–tandem mass spectrometry. Gene network analysis was performed using the ANDSystem platform to reconstruct gene and protein interaction networks linking altered metabolites to membrane receptors, lipid raft proteins, and signaling pathways. Overrepresentation analysis of biological processes was applied to identify enriched functional categories.

Results

THz exposure did not affect cell viability but induced significant alterations in purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway. Network analysis revealed that these metabolic changes were associated with membrane raft reorganization and receptor-mediated signaling involving epidermal growth factor receptor and G-protein subunits. Additional effects were observed in pathways related to chromatin organization and post-translational regulation.

Conclusions

Exposure of SK-MEL-28 melanoma cells to 2.3 THz radiation produces coordinated alterations in metabolic and regulatory networks without affecting cell viability. Metabolomic profiling reveals pronounced modulation of purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway, while bioinformatic analysis links these changes to processes of chromatin organization, G-protein–mediated signaling, and post-translational regulation. Gene network reconstruction indicates that lipid raft–associated receptors and enzymes act as central mediators of these responses, suggesting that cellular membrane proteins may serve as sensitive interfaces for THz irradiation perception and transduction. The observed remodeling of nucleotide and energy metabolism suggests an adaptive, non-thermal reprogramming of biochemical pathways, enabling cells to maintain homeostasis under electromagnetic stimulation.