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To identify natural compounds with anticancer potential against CRC and elucidate their action mechanisms, the cytotoxicity of 37 natural compounds was evaluated against the HCT116, leading to the identification of conferone as the lead candidate. Its anti\u2010migratory and anti\u2010invasive effects were evaluated in HCT116, Colo205, and SW480 cells. The interactions between conferone and focal adhesion kinase (FAK) were assessed through protein expression analysis and molecular docking. Glutaminolysis regulation was determined by LC\u2013MS\/MS, and related enzyme levels were detected by western blotting. Conferone inhibited migration and invasion in all three CRC cell lines, though it showed limited anti\u2010proliferative activity. At 10\u2009\u03bcM, conferone reduced FAK and p\u2010FAK (Tyr397) protein levels, reversing the epithelial\u2010mesenchymal transition. Docking analysis confirmed direct FAK binding and predicted inhibition of its phosphorylation, with greater affinity than the FAK inhibitor 1,2,4,5\u2010benzene tetramine tetrahydrochloride. Conferone also downregulated glutaminase and glutamate\u2013ammonia ligase, increasing glutamine and decreasing glutamic acid. Additionally, it suppressed c\u2010raf phosphorylation and reduced c\u2010Myc expression, blocking glutaminolysis\u2010driven metabolism. These findings highlight conferone as a potential therapeutic agent that targets FAK, alters metabolic reprogramming, and impedes CRC progression.<\/jats:p>","DOI":"10.1111\/jcmm.71165","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:00:27Z","timestamp":1777521627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibitory Activity of Conferone on\n                    <scp>FAK<\/scp>\n                    Activity and Glutamine Metabolism in Human Colorectal Cancer"],"prefix":"10.1111","volume":"30","author":[{"given":"Hien Thi My","family":"Ong","sequence":"first","affiliation":[{"name":"Centre for Advanced Biomolecular Recognition Korea Institute of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"},{"name":"Division of Bio\u2010Medical Science &amp; Technology KIST School, University of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eda","family":"Ates","sequence":"additional","affiliation":[{"name":"Centre for Advanced Biomolecular Recognition Korea Institute of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"},{"name":"Division of Bio\u2010Medical Science &amp; Technology KIST School, University of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeyong","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Yonsei University, 50 Yonsei\u2010Ro, Seodaemun\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Soo","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Yonsei University, 50 Yonsei\u2010Ro, Seodaemun\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Chul","family":"Pyun","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Yonsei University, 50 Yonsei\u2010Ro, Seodaemun\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-2037","authenticated-orcid":false,"given":"Min\u2010Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Centre for Advanced Biomolecular Recognition Korea Institute of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"},{"name":"Division of Bio\u2010Medical Science &amp; Technology KIST School, University of Science and Technology, 5, Hwarang\u2010Ro 14\u2010Gil, Seongbuk\u2010Gu  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010021\u201003888\u2010w"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010019\u20101083\u20100"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2021.5856"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010024\u201012905\u20103"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1199211"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14122928"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2010.12.010"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109142"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2018.10.011"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201004773\u20101"},{"key":"e_1_2_12_13_1","volume-title":"Ed., the Heterogeneity of Cancer Metabolism, Vol. 1311. 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