{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:13:08Z","timestamp":1781874788940,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>5\u2010Fluorouracil (5\u2010FU) is a first\u2010line chemotherapy for gastric cancer (GC), but its efficacy is often limited by acquired resistance mediated by upregulation of thymidylate synthase (TS). Sodium butyrate (NaB), a microbiota\u2010derived short\u2010chain fatty acid (SCFA), has shown potential in colorectal cancer, but its role in overcoming 5\u2010FU resistance in GC remains undefined.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Therefore, we investigated the molecular mechanisms of NaB in GC cell lines (AGS and KATO\u2010III) by evaluating cell viability, migration, apoptosis, mitochondrial membrane potential, cell cycle, and gene expressions related to DNA synthesis, cell cycle, and cellular stress. NaB decreased cell viability, impaired cellular aggregation, and induced apoptosis and mitochondrial dysfunction. Furthermore, NaB synergized with 5\u2010FU, enhancing growth inhibition and apoptotic effects. Notably, NaB significantly downregulated TS expression at both mRNA and protein levels and also reduced gene expression such as <jats:italic>TK1<\/jats:italic> and <jats:italic>FOXM1<\/jats:italic>. Cell\u2010cycle analysis indicated distinct responses between AGS (p53\u2010wild\u2010type) and KATO\u2010III (p53\u2010null) cells.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>In conclusion, as a fermentation product of dietary fiber, NaB represents an accessible nutritional adjuvant. Dietary or probiotic strategies to boost systemic butyrate levels could be combined with standard chemotherapy to improve response rates, mitigate resistance, and support patient outcomes in GC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.70152","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T04:54:46Z","timestamp":1750049686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sodium Butyrate Enhances 5\u2010Fluorouracil Sensitivity Through Thymidylate Synthase Regulation and Cell\u2010Cycle Modulation in Gastric Cancer"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6566-3972","authenticated-orcid":false,"given":"Nayeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Science Education Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5326-9124","authenticated-orcid":false,"given":"Changwon","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Science Education Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.068"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw350"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041040305"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-022-01864-z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14306"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26822"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665120006916"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3920\/BM2020.0057"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.886902"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2307542"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i20.2826"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06553.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031572"},{"key":"e_1_2_7_17_1","first-page":"665","article-title":"Detection of Poly(ADP\u2010Ribose) Polymerase Cleavage in Response to Treatment With Topoisomerase I Inhibitors: A Potential Surrogate End Point to Assess Treatment Effectiveness","volume":"5","author":"Whitacre C. 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