γ-Tocotrienol-Inhibited Cell Proliferation of Human Gastric Cancer by Regulation of Nuclear Factor-κB Activity.

Abstract

γ-Tocotrienol (γ-T3) exhibits the activity of anticancer via regulating cell signaling pathways. Nuclear factor-κB (NF-κB), one of the crucial pro-inflammatory factors, is involved in the regulation of cell proliferation, apoptosis, invasion, and migration of tumor. In the present study, NF-κB activity inhibited by γ-T3 was investigated in gastric cancer cells. Cell proliferation, NF-κB activity, active protein phosphatase type 2A (PP2A), and ataxia-telangiectasia mutated (ATM) protein were explored using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), methylene blue, enzyme-linked immunosorbent assay (ELISA), malachite green, luciferase, and Western blotting assays. The effects of γ-T3 on tumor growth and the expression of NF-κB and PP2A proteins were also further examined by implanting human gastric cancer cells in a BALB/c nude mouse model. The results showed that γ-T3 significantly inhibited the cell proliferation and attenuated the NF-κB activity in vitro and in vivo. γ-T3 dramatically increased PP2A activity and protein expression, which suppressed ATM phosphorylation and its translocation to the cytoplasm in gastric cancer cells. Thus, our findings may provide mechanistic insight into effects of γ-T3 on the regulation of NF-κB activity by a PP2A-dependent mechanism and suggest that PP2A may serve as a molecular target for a potential chemopreventive agent.