The Anti Proliferative Effect Of Palm Oil Gamma-Tocotrienol Involves Alterations In Mek-2 And Erk-2 Protein Expressions In Caski Cells

Background: Vitamin E is a potent growth inhibitor of various cancer cell types in vitro and in vivo. The cell death mechanism is believed to be via cell cycle blockage, differentiation, and apoptosis.Objectives: To determine the possible involvement of protein expression of MEK-2 and ERK-2 in the cell death mechanism induced by palm oil gamma-tocotrienol and alpha-tocopherol in human cervical cancer cell line, CaSki cells.Methods: In this study, we tested the effect of gamma-tocotrienol and alpha-tocopherol on the proliferation and apoptosis in CaSki cells. Western blot analysis was used to determine the involvement of MEK-2 and ERK-2 in regulating the cell death mechanism.Results: Gamma-tocotrienol and alpha-tocopherol efficiently inhibited the proliferation of CaSki cells by 85.2% to 90.8% (p<0.01, n=4) and 10.2% to 39.1% (p<0.01, n=4) beginning at 100 mu M and 50 mu M respectively. The possible cell death mechanism induced by both compounds may be due to apoptosis as confirmed by the presence of cellular DNA fragments separated by electrophoresis and enhancement of apoptotic activity. Treatment with gamma-tocotrienol at 150 mu M markedly decreased the protein expression of MEK-2 and ERK-2 at 12 hours and 18 hours. In contrast, treatment with alpha-tocopherol at 300 mu M has no effect on both protein expressions.Conclusion: The transient decreases in the protein expression of MEK-2 and ERK-2 suggested that the anti proliferative effect of gamma-tocotrienol might involve alteration of the proliferative signaling cascade.