Tian, Yichun, Wang, Xian, Lu, Zhaoxin, Mi, Yaqing, Zhou, Shaobo ORCID: https://orcid.org/0000-0001-5214-2973 and Xu, Weili (2026) γ-Tocotrienol inhibits HeLa cell proliferation likely via modulation of the PI3K/AKT/mTOR signaling pathway. Frontiers Nutrition, 13:1804277. pp. 1-13. ISSN 2296-861X (Online) (doi:10.3389/fnut.2026.1804277)

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Abstract

Introduction: γ-Tocotrienol (γ-T3), a natural isoform of vitamin E, has demonstrated anticancer activity; however, its underlying molecular mechanisms remain incompletely understood. This study investigated whether γ-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.
Methods: HeLa cells were treated with γ-T3 at different concentrations (0-80 μmol/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 γ-T3 and WM was also evaluated.Results: γ-T3 treatment reduced the expression and phosphorylation of PI3K, AKT and mTOR, as well as downstream targets p70S6K and 4E-BP1. γ-T3 also decreased proliferation-associated proteins cyclin D1 and c-Myc. The inhibitory effect of γ-T3 at 40 μmol/L was comparable to that of WM. Functionally, γ-T3 suppressed cell proliferation, induced G0/G1 phase arrest with a reduced S-phase fraction, and promoted apoptosis in HeLa cells. Co-treatment with γ-T3 and WM further enhanced growth inhibition and apoptosis compared with either treatment alone.
Discussion: These findings indicate that γ-T3 inhibits HeLa cell proliferation, at least in part, via suppression of the PI3K/AKT/mTOR signaling pathway. This supports further evaluation of γ-T3 as a nutrition-relevant bioactive compound for cancer prevention research and as a potential adjunct to therapy.

Item Type:	Article
Additional Information:	The author(s) declared that financial support was received for this work and/or its publication.
Uncontrolled Keywords:	γ-tocotrienol, cervical cancer, proliferation, apoptosis, PI3K/AKT/mTOR signaling pathway
Subjects:	Q Science > Q Science (General) R Medicine > R Medicine (General)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	17 Apr 2026 09:57
URI:	https://gala.gre.ac.uk/id/eprint/52848

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