Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway
Journal
Integrative Cancer Therapies
Journal Volume
9
Journal Volume
9
Journal Issue
1
Journal Issue
1
Pages
66-72
Start Page
66
End Page
72
ISSN
1552695X
Date Issued
2010-03
Author(s)
Wu, Shu-Jing
Abstract
Tocotrienols 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.
Subjects
Antiproliferative
Apoptosis
Cell cycle
HeLa cells
Tocotrienols
SDGs
Other Subjects
alpha 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; Tocotrienols
Type
journal article