{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:21:56Z","timestamp":1776349316836,"version":"3.51.2"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\u03b3-Tocotrienol (\u03b3-T3), a natural isoform of vitamin E, has demonstrated anticancer activity; however, its underlying molecular mechanisms remain incompletely understood. This study investigated whether \u03b3-T3 suppresses human cervical cancer HeLa cell growth through modulation of the phosphatidylinositol 3-kinase\/protein kinase B\/mammalian target of rapamycin (PI3K\/AKT\/mTOR) signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HeLa cells were treated with \u03b3-T3 at different concentrations (0-80 \u03bcmol\/L). Protein expression and phosphorylation levels of PI3K, AKT, mTOR and downstream effectors (p70S6K and 4E-BP1) were analyzed. Cell proliferation, cell cycle distribution and apoptosis were assessed. Wortmannin (WM), a selective PI3K inhibitor, was used as a comparator. Combined treatment with \u03b3-T3 and WM was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u03b3-T3 treatment reduced the expression and phosphorylation of PI3K, AKT and mTOR, as well as downstream targets p70S6K and 4E-BP1. \u03b3-T3 also decreased proliferation-associated proteins cyclin D1 and c-Myc. The inhibitory effect of \u03b3-T3 at 40 \u03bcmol\/L was comparable to that of WM. Functionally, \u03b3-T3 suppressed cell proliferation, induced G0\/G1 phase arrest with a reduced S-phase fraction, and promoted apoptosis in HeLa cells. Co-treatment with \u03b3-T3 and WM further enhanced growth inhibition and apoptosis compared with either treatment alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate that \u03b3-T3 inhibits HeLa cell proliferation, at least in part, via suppression of the PI3K\/AKT\/mTOR signaling pathway. This supports further evaluation of \u03b3-T3 as a nutrition-relevant bioactive compound for cancer prevention research and as a potential adjunct to therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1804277","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T13:38:00Z","timestamp":1776346680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b3-Tocotrienol inhibits HeLa cell proliferation likely via modulation of the PI3K\/AKT\/mTOR signaling pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Yichun","family":"Tian","sequence":"first","affiliation":[{"name":"Innovation Research Center for Special Food-Medicine and Biochemical Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology","place":["Harbin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Research Center for Special Food-Medicine and Biochemical Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology","place":["Harbin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoxin","family":"Lu","sequence":"additional","affiliation":[{"name":"Innovation Research Center for Special Food-Medicine and Biochemical Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology","place":["Harbin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqing","family":"Mi","sequence":"additional","affiliation":[{"name":"Innovation Research Center for Special Food-Medicine and Biochemical Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology","place":["Harbin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Science, Faculty of Engineering and Science, University of Greenwich, Central Avenue","place":["Chatham, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weili","family":"Xu","sequence":"additional","affiliation":[{"name":"Innovation Research Center for Special Food-Medicine and Biochemical Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology","place":["Harbin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1007\/s00761-020-00760-3","article-title":"Surgical treatment of cervical cancer","volume":"26","author":"Fehm","year":"2020","journal-title":"Onkologe"},{"key":"B3","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13048-020-00626-7","article-title":"Functional activities of beta-glucans in the prevention or treatment of cervical cancer","volume":"13","author":"Chaichian","year":"2020","journal-title":"J Ovarian Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"125","DOI":"10.2174\/138920112798868610","article-title":"Cancer chemoprevention by dietary phytochemicals: promises and pitfalls","volume":"13","author":"Priyadarsini","year":"2012","journal-title":"Curr Pharm Biotechnol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/nrc1189","article-title":"Cancer chemoprevention with dietary phytochemicals","volume":"3","author":"Surh","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrc3017","article-title":"Molecular targets of phytochemicals for cancer prevention","volume":"11","author":"Lee","year":"","journal-title":"Nat Rev Cancer. 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