Abstract
γ-Tocotrienol (γ-T3) exhibits the activity of anti-cancer via regulating cell signaling pathways. Nuclear factor-kB (NF-kB), one of crucial pro-inflammatory factors, involved in the regulation of cell proliferation, apoptosis, invasion and migration of tumor. In the present study, NF-kB activity inhibited by γ-T3 was investigated in gastric cancer cells. Cell proliferation, NF-kB activity, active protein phosphatase type 2A (PP2A), and ataxia-telangiectasia mutated (ATM) protein were explored using MTT, methylene blue, ELISA, malachite green, luciferase and Western blotting assays. The effects of γ-T3 on tumor growth, the expression of NF-kB 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-kB 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-kB activity by a PP2A-dependent mechanism and suggest that PP2A may serve as a molecular target for a potential chemopreventive agent.