Work

γ-Tocotrienol inhibits HeLa cell proliferation likely via modulation of the PI3K/AKT/mTOR signaling pathway

Year: 2026

Type: article

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.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2026.1804277

Authors: Yichun Tian, Xian Wang, Zhaoxin Lu, Yaqing Mi, Shaobo Zhou, Weili Xu

Institutions: Harbin Institute of Technology, University of Greenwich

Language: English

Topic: PI3K/AKT/mTOR signaling in cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801