Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway.
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 alpha-, gamma- and delta-tocotrienols (alphaT3, gammaT3, and deltaT3), and alpha-tocopherol (alphaT) in human cervical carcinoma (HeLa) cells. Their mechanism(s) of action on cell cycle signaling pathway were also investigated.


RESULTS
3.19 +/- 0.05 microM) and gammaT3 (IC(50): 2.85 +/- 0.07 microM) was more potent than deltaT3 (IC(50): >100 microM) and alphaT (IC(50): 69.46 +/- 3.01 microM). Both alphaT3 and gammaT3 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 microM, alphaT3 downregulated the expression of cyclin D3, p16, and CDK6, while having no effect on cyclin D1, p15, p21, p27, and CDK4 expression. However, gammaT3 showed no effect on these proteins. The induction of HeLa cell apoptosis by alphaT3 and gammaT3 appeared to be associated with the expression of IL-6, but not the other cytokines (IFN-gamma, IL-2, and IL-10).Taken together, the results suggest that alphaT3 and gammaT3 are more effective than deltaT3 and alphaT 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.
Wu
Shu-Jing
SJ
Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
Ng
Lean-Teik
LT
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D024508:Tocotrienols / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016207:Cytokines; D024508:Tocotrienols; D024502:alpha-Tocopherol