2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo

Abstract

Background: Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated. Methods: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models. Results: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model. Conclusions: 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients.