{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:57:35Z","timestamp":1785430655436,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022790","name":"Hector Foundation II","doi-asserted-by":"crossref","award":["MED1710"],"award-info":[{"award-number":["MED1710"]}],"id":[{"id":"10.13039\/501100022790","id-type":"DOI","asserted-by":"crossref"}]},{"award":["MED1710"],"award-info":[{"award-number":["MED1710"]}],"id":[{"id":"https:\/\/ror.org\/05jwkgv16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cancer-related cachexia is primarily characterized by systemic inflammation and progressive muscle wasting, which is why a high-protein diet (from 1.2 to 1.5 g\/kg\/day) is commonly recommended. However, concerns remain that an excessive supply of amino acids could promote tumor growth due to the metabolic flexibility of cancer cells, thereby favoring proliferation and survival. Systematic evidence addressing these concerns under controlled conditions for various types of cancer cells remains limited and inconclusive. Methods: We investigated the short-term effects of all 20 amino acids at both moderate (2\u00d7) and high (10\u00d7) concentrations to evaluate three key oncological endpoints in four human cancer cell lines: MDA-MB-231 (breast), HT29 (colorectal), PC3 (prostate), and PANC-1 (pancreatic). Cell proliferation was assessed by BrdU incorporation, metabolic activity by WST-1 assay, and apoptosis signaling by caspase-3\/7 activity measurement. Results: Amino acid supplementation was not associated with a significant change in proliferation at either concentration across all four cell lines studied. Metabolic activity showed only minor variations throughout, with PC3 cells exhibiting slightly greater variability, although this did not reach statistical significance. Caspase-3\/7 activity remained largely unchanged under all conditions; however, high-concentration lysine induced an approximately 2.5-fold increase in PANC1 cells, which was not statistically significant. Conclusions: These findings suggest that short-term exposure to individual amino acids, even at supraphysiological conditions, does not acutely enhance proliferative activity in the cancer cell lines studied, supporting the rationale for adequate protein and amino acid intake in patients with cancer cachexia.<\/jats:p>","DOI":"10.3390\/nu18132125","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"2125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Individual Amino Acid Supplementation Does Not Enhance Short-Term Proliferation of Selected Cancer Cell Lines In Vitro: Potential Implications for Nutritional Support in Cancer Cachexia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1778-1056","authenticated-orcid":false,"given":"Walburga","family":"Dieterich","sequence":"first","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7513-0698","authenticated-orcid":false,"given":"Rashmita","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1114-8444","authenticated-orcid":false,"given":"Abdulhadi","family":"Suwandi","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-5346","authenticated-orcid":false,"given":"Rabia \u00dclk\u00fc","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4344-1474","authenticated-orcid":false,"given":"Markus F.","family":"Neurath","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-7488","authenticated-orcid":false,"given":"Yurdag\u00fcl","family":"Zopf","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Hector-Center for Nutrition, Exercise and Sports, Department of Medicine 1, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100282","DOI":"10.1016\/j.advnut.2024.100282","article-title":"Prevalence of and Survival with Cachexia among Patients with Cancer: A Systematic Review and Meta-Analysis","volume":"15","author":"Takaoka","year":"2024","journal-title":"Adv. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mariean, C.R., Tiuca, O.M., Mariean, A., and Cotoi, O.S. (2023). Cancer Cachexia: New Insights and Future Directions. Cancers, 15.","DOI":"10.3390\/cancers15235590"},{"key":"ref_3","first-page":"3007","article-title":"Protein intake and muscle mass maintenance in patients with cancer types with high prevalence of sarcopenia: A systematic review","volume":"30","author":"Coutinho","year":"2022","journal-title":"Support. Care Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.clnu.2016.07.015","article-title":"ESPEN guidelines on nutrition in cancer patients","volume":"36","author":"Arends","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kim, D., and Park, Y. (2020). Amount of Protein Required to Improve Muscle Mass in Older Adults. Nutrients, 12.","DOI":"10.3390\/nu12061700"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Corsetti, G., Pasini, E., Romano, C., and Dioguardi, F.S. (2025). Amino Acids Supplementation in Cancer: What Do We Feed, the Patient or the Tumor?. Nutrients, 17.","DOI":"10.3390\/nu17172813"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2300577","DOI":"10.1002\/mnfr.202300577","article-title":"Bckdk-Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia","volume":"68","author":"Chen","year":"2024","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70067","DOI":"10.1111\/apha.70067","article-title":"Branched-Chain Amino Acids and Di-Alanine Supplementation Attenuates Muscle Atrophy in a Murine Model of Cancer Cachexia","volume":"241","author":"Colardo","year":"2025","journal-title":"Acta Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s12276-023-00971-9","article-title":"Targeting glutamine metabolism as a therapeutic strategy for cancer","volume":"55","author":"Jin","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115529","DOI":"10.1016\/j.celrep.2025.115529","article-title":"Amino acids in cancer: Understanding metabolic plasticity and divergence for better therapeutic approaches","volume":"44","author":"Do","year":"2025","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s12943-025-02523-3","article-title":"Amino acids metabolism: A potential target for cancer treatment","volume":"24","author":"Ren","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1111\/febs.14081","article-title":"Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation","volume":"284","author":"Bonfili","year":"2017","journal-title":"FEBS J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41421-025-00791-3","article-title":"Caspases: Structural and molecular mechanisms and functions in cell death, innate immunity, and disease","volume":"11","author":"Nadendla","year":"2025","journal-title":"Cell Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63679","DOI":"10.18632\/oncotarget.11626","article-title":"Leucine deprivation inhibits proliferation and induces apoptosis of human breast cancer cells via fatty acid synthase","volume":"7","author":"Xiao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1038\/s44318-025-00505-1","article-title":"mTORC1 senses glutamine and other amino acids through GCN2","volume":"44","author":"Figlia","year":"2025","journal-title":"EMBO J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hara, F., Nagasaki, R., Minami, R., Izutani, T., Yoshida, T., Arai, A., Nihei, A., Sakurai, N., and Ohno, S. (2024). Survey on adverse events associated with drug therapy for breast cancer patients. BMC Womens Health, 24.","DOI":"10.1186\/s12905-024-03355-x"},{"key":"ref_17","first-page":"2431","article-title":"Correction to: Influence of cancer and acute inflammatory disease on taste perception: A clinical pilot study","volume":"28","author":"Schalk","year":"2020","journal-title":"Support. Care Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41416-019-0620-5","article-title":"New aspects of amino acid metabolism in cancer","volume":"122","author":"Vettore","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"0335","DOI":"10.34133\/research.0335","article-title":"Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism","volume":"7","author":"Xiao","year":"2024","journal-title":"Research"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1038\/srep03041","article-title":"Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival","volume":"3","author":"Feizi","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature22056","article-title":"Modulating the therapeutic response of tumours to dietary serine and glycine starvation","volume":"544","author":"Maddocks","year":"2017","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2049-3002-2-6","article-title":"Leucine supplementation differentially enhances pancreatic cancer growth in lean and overweight mice","volume":"2","author":"Liu","year":"2014","journal-title":"Cancer Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6777","DOI":"10.1038\/s41467-023-42458-1","article-title":"Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth","volume":"14","author":"Tombari","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Akbay, B., Omarova, Z., Trofimov, A., Sailike, B., Karapina, O., Moln\u00e1r, F., and Tokay, T. (2024). Double-Edge Effects of Leucine on Cancer Cells. Biomolecules, 14.","DOI":"10.20944\/preprints202409.0126.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.ircmb.2022.08.001","article-title":"Targeting amino acid metabolism in cancer","volume":"373","author":"Safrhansova","year":"2022","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1158\/1078-0432.CCR-14-1200","article-title":"Targeting Glutamine Metabolism in Breast Cancer with Aminooxyacetate","volume":"21","author":"Korangath","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.2174\/0929867329666220817141227","article-title":"Cysteine Metabolism in Tumor Redox Homeostasis","volume":"30","author":"Fan","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1038\/s41467-020-17181-w","article-title":"Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Burch, T.C., Isaac, G., Booher, C.L., Rhim, J.S., Rainville, P., Langridge, J., Baker, A., and Nyalwidhe, J.O. (2015). Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134206"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fi\u00f1ones, R.R., Yeargin, J., Lee, M., Kaur, A.P., Cheng, C., Sun, P., Wu, C., Nguyen, C., Wang-Rodriguez, J., and Meyer, A.N. (2013). Early human prostate adenocarcinomas harbor androgen-independent cancer cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074438"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wei, Z., Liu, X., Cheng, C., Yu, W., and Yi, P. (2020). Metabolism of Amino Acids in Cancer. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.603837"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5680968","DOI":"10.1155\/2021\/5680968","article-title":"High Expression Levels of SLC38A1 Are Correlated with Poor Prognosis and Defective Immune Infiltration in Hepatocellular Carcinoma","volume":"2021","author":"Liu","year":"2021","journal-title":"J. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00726-015-2084-0","article-title":"Intimacy and a deadly feud: The interplay of autophagy and apoptosis mediated by amino acids","volume":"47","author":"Wu","year":"2015","journal-title":"Amino Acids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1530\/ERC-15-0192","article-title":"Glutamine promotes ovarian cancer cell proliferation through the mTOR\/S6 pathway","volume":"22","author":"Yuan","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/s41419-022-05346-y","article-title":"Limiting glutamine utilization activates a GCN2\/TRAIL-R2\/Caspase-8 apoptotic pathway in glutamine-addicted tumor cells","volume":"13","author":"Yerbes","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ji, Y., Li, M., Chang, M., Liu, R., Qiu, J., Wang, K., Deng, C., Shen, Y., Zhu, J., and Wang, W. (2022). Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants, 11.","DOI":"10.3390\/antiox11091686"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C1837","DOI":"10.1152\/ajpcell.00808.2024","article-title":"Inflammation in cancer cachexia: Still the central tenet or just another player?","volume":"328","author":"Iaia","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/s42255-025-01265-2","article-title":"Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice","volume":"7","author":"Liu","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112030","DOI":"10.1016\/j.isci.2025.112030","article-title":"Pre-cachectic changes in amino acid homeostasis precede activation of eIF2\u03b1 signaling in the liver at the onset of C26 cancer-induced cachexia","volume":"28","author":"Chaouki","year":"2025","journal-title":"iScience"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:24:22Z","timestamp":1783052662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":39,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18132125"],"URL":"https:\/\/doi.org\/10.3390\/nu18132125","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}