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Although understanding of metabolic reprogramming in melanoma has advanced, the connection between metabolic alterations and metastatic capacity remains incomplete.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to characterize the metabolic profiles of human melanoma cell lines with high (HT168-M1) and low (WM983B) metastatic potential, and to compare them with each other and also with the metabolic profile of normal human fibroblasts (MRC-5), in order to identify key metabolites and metabolic pathways associated with metastatic behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Non-targeted metabolomic profiling using \u00b9H-NMR spectroscopy was applied to hydrophilic extracts of the three cell lines. Multivariate statistical analyses (PCA and PLS-DA) were used to identify discriminating metabolites, and pathway analysis was performed to determine altered metabolic networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Several metabolic pathways were significantly altered in melanoma cells compared to fibroblasts, including starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism. Metabolites showing more than two-fold differences included elevated UDP-glucose, ATP, glycerophosphocholine, GTP, creatine and glutathione in the melanoma cells, and reduced glucose, glutamine and 1-methylnicotinamide in fibroblasts. Comparison of the metabolites of melanoma cell lines with differing metastatic potential revealed changes in taurine and hypotaurine, \u03b2-alanine-, glutathione-, and amino acid metabolism. Metabolites showing the largest concentration changes were UDP-glucose, glutathione, NAD\n                      <jats:sup>+<\/jats:sup>\n                      , alanine and \u03b2-alanine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metabolomic profiling revealed distinct metabolic reprogramming between melanoma and normal fibroblasts, characterized by enhanced glycolysis and glutathione-dependent antioxidant defense. Highly metastatic melanoma cells demonstrated stronger redox adaptation and altered amino acid utilization, with elevated glutathione and glutamate and reduced NAD\u207a and pyruvate, indicating a metabolic shift toward oxidative stress resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0352639","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:38:27Z","timestamp":1782927507000},"page":"e0352639","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic profiling of human melanoma cell lines with high and low metastatic capacity by 1H-NMR spectroscopy"],"prefix":"10.1371","volume":"21","author":[{"given":"Nima Rezvani","family":"Kakhki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita","family":"Heged\u0171s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"T\u00f3v\u00e1ri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-8435","authenticated-orcid":true,"given":"Arash","family":"Mirzahosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Nosz\u00e1l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-9486","authenticated-orcid":true,"given":"M\u00e1rta","family":"Kraszni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"issue":"21","key":"pone.0352639.ref001","doi-asserted-by":"crossref","first-page":"15881","DOI":"10.3390\/ijms242115881","article-title":"Cutaneous 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