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Leucine plays a pivotal role in stimulating muscle protein synthesis, along with isoleucine and valine, as the group of branched-chain amino acids, making them one of the most popular dietary supplements for athletes and gym-goers. The individual effects of leucine, however, have not been fully clarified, as most of the studies so far have focused on the grouped effects of branched-chain amino acids. In recent years, leucine and its metabolites have been shown to stimulate muscle protein synthesis mainly via the mammalian target of the rapamycin complex 1 signaling pathway, thereby improving muscle atrophy in cancer cachexia. Interestingly, cancer research suggests that leucine may have either anti-cancer or pro-tumorigenic effects. In the current manuscript, we aim to review leucine\u2019s roles in muscle protein synthesis, tumor suppression, and tumor progression, specifically summarizing the molecular mechanisms of leucine\u2019s action. The role of leucine is controversial in hepatocellular carcinoma, whereas its pro-tumorigenic effects have been demonstrated in breast and pancreatic cancers. In summary, leucine being used as nutritional supplement for athletes needs more attention, as its pro-oncogenic effects may have been identified by recent studies. Anti-cancer or pro-tumorigenic effects of leucine in various cancers should be further investigated to achieve clear conclusions.<\/jats:p>","DOI":"10.3390\/biom14111401","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T03:57:34Z","timestamp":1730692654000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Double-Edge Effects of Leucine on Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-170X","authenticated-orcid":false,"given":"Burkitkan","family":"Akbay","sequence":"first","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9207-0693","authenticated-orcid":false,"given":"Zhannur","family":"Omarova","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6745-6035","authenticated-orcid":false,"given":"Alexander","family":"Trofimov","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayan","family":"Sailike","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orynbassar","family":"Karapina","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-4233","authenticated-orcid":false,"given":"Ferdinand","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-3301","authenticated-orcid":false,"given":"Tursonjan","family":"Tokay","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1002\/anie.201208344","article-title":"Nonproteinogenic Amino Acid Building Blocks for Nonribosomal Peptide and Hybrid Polyketide Scaffolds","volume":"52","author":"Walsh","year":"2013","journal-title":"Angew. 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