Wu, Shu-JingShu-JingWuLEAN-TEIK HUANG2018-09-102018-09-102010-03https://www.scopus.com/pages/publications/77953922267?inwardhttp://scholars.lib.ntu.edu.tw/handle/123456789/356832Tocotrienols of palm oil have been shown to possess potent neuroprotective, antioxidative, anticancer, and cholesterol-lowering activities. In this study, the authors examined the antiproliferative effects of α-, γ- and δ-tocotrienols (αT3, γT3, and δT3), and α-tocopherol (αT) in human cervical carcinoma (HeLa) cells. Their mechanism(s) of action on cell cycle signaling pathway were also investigated. Results showed that the antiproliferative effect of αT3 (IC50: 3.19 ± 0.05 μM) and γT3 (IC50: 2.85 ± 0.07 μM) was more potent than δT3 (IC50: >100 μM) and αT (IC50: 69.46 ± 3.01 μM). Both αT3 and γT3 also demonstrated a dose-dependent and time-dependent induction of cell death.They caused cell cycle arrest at G2/M phase and triggered apoptosis as displayed by the externalization of annexin V-targeted phosphatidylserine and accumulation of sub-G1 peak. At a concentration of 3 μM, αT3 downregulated the expression of cyclin D3, p16, and CDK6, while having no effect on cyclin D1, p15, p21, p27, and CDK4 expression. However, γT3 showed no effect on these proteins. The induction of HeLa cell apoptosis by αT3 and γT3 appeared to be associated with the expression of IL-6, but not the other cytokines (IFN-γ, IL-2, and IL-10).Taken together, the results suggest that αT3 and γT3 are more effective than δT3 and αT in inhibiting HeLa cell proliferation, and their mode of action could be through the upregulation of IL-6, and the downregulation of cyclin D3, p16, and CDK6 expression in the cell cycle signaling pathway.AntiproliferativeApoptosisCell cycleHeLa cellsTocotrienols[SDGs]SDG3alpha tocopherol; alpha tocotrienol; antineoplastic agent; cyclin D1; cyclin D3; cyclin dependent kinase 4; cyclin dependent kinase 6; delta tocopherol; delta tocotrienol; gamma interferon; gamma tocotrienol; interleukin 10; interleukin 2; interleukin 6; lipocortin 5; phosphatidylserine; protein p15; protein p16; protein p21; protein p27; tocopherol; unclassified drug; alpha tocopherol; cell cycle protein; cyclin dependent kinase inhibitor; cytokine; antineoplastic activity; apoptosis; article; cancer growth; cancer inhibition; cell cycle G1 phase; cell cycle G2 phase; cell cycle M phase; cell death; cell proliferation; competitive inhibition; concentration (parameters); controlled study; dose response; down regulation; drug cytotoxicity; female; HeLa cell; human; human cell; IC 50; molecular dynamics; priority journal; protein expression; signal transduction; upregulation; uterine cervix carcinoma; cell cycle; cell proliferation; cell survival; drug effect; drug screening; HeLa cell; metabolism; physiology; alpha-Tocopherol; Apoptosis; Cell Cycle; Cell Cycle Proteins; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor Proteins; Cytokines; Down-Regulation; Drug Evaluation, Preclinical; Hela Cells; Humans; Signal Transduction; Tocotrienolsjournal article10.1177/15347354093577572-s2.0-77953922267