γ‐Tocotrienol enhances autophagy of gastric cancer cells by the regulation of GSK3β/β‐Catenin pathway

Abstract

Abstractγ‐Tocotrienol (γ‐T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ‐T3 has effects on anti‐inflammation, anti‐oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ‐T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ‐T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ‐T3 (0–90 μmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose‐dependent manner. Autophagy was increased in MKN45 cells treated with γ‐T3 (0–45 μmol/L), especially at a dose of 30 μmol/L for 24 h. These effects were reversed by 3‐methyladenine pretreatment. Furthermore, γ‐T3 (30 μmol/L) also significantly downregulated the expression of pGSK‐3β (ser9) and β‐catenin protein in MKN45 cells, and γ‐T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK‐3β inhibitor‐CHIR‐99021 reversed the negative regulation of GSK‐3β/β‐Catenin signaling and autophagy. Our findings indicated that γ‐T3 enhances autophagy in gastric cancer cells mediated by GSK‐3β/β‐Catenin signaling, which provides new insights into the role of γ‐T3 enhancing autophagy in gastric cancer.