{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:13:56Z","timestamp":1779909236748,"version":"3.53.1"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Introduction: There is evidence for the anticancer effects of L-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear. Methods: Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using [\u00b9\u00b3C\u2086] L-arginine. Results: In OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline\/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle. Conclusion: Arginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine.<\/jats:p>","DOI":"10.1159\/000543006","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T17:21:24Z","timestamp":1733851284000},"page":"1-32","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic analysis of three-dimensional cultured gastrointestinal cancer cells suggests that L-arginine inhibits tumor growth by affecting the urea cycle"],"prefix":"10.1159","author":[{"given":"Eri","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Taniura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Mukaisho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kageyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Noujima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Ishigaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Kushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2024,12,10]]},"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/pat\/article-pdf\/doi\/10.1159\/000543006\/4312243\/000543006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/pat\/article-pdf\/doi\/10.1159\/000543006\/4312243\/000543006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:05:01Z","timestamp":1745420701000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000543006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000543006","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.27979919","asserted-by":"subject"}]},"ISSN":["1015-2008","1423-0291"],"issn-type":[{"value":"1015-2008","type":"print"},{"value":"1423-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,10]]}}}