title: Akt/AMPK/mTOR pathway was involved in the autophagy induced by vitamin E succinate in human gastric cancer SGC-7901 cells.
abstract: Vitamin E succinate (VES), a derivative of vitamin E, is a promising cancer chemopreventive agent that inhibits tumor promotion by inducing apoptotic cell death. The effects of VES on autophagy, an intricate programmed process which helps cells survive in some stressed situations by degrading some cytoplasmic material, are unclear. When human gastric cancer cells SCG-7901 were exposed to VES, both the level of microtubule-associated protein 1 light chain 3 and the yeast ATG6 homolog Beclin-1 increased, and related autophagy genes were activated, thereby suggesting that autophagy was induced by VES. We also observed that VES-induced autophagy was accompanied by the activation of AMP-activated protein kinases (AMPK). VES-induced autophagy decreased when AMPK was inhibited by using small interfering RNA (siRNA), thereby suggesting that VES-induced autophagy is mediated by AMPK. Moreover, further studies revealed that the decreased activity of mammalian target of rapamycin (mTOR) and its downstream targets P70S6K and 4EBP-1 were involved in VES-activated autophagy associated with AMPK activation. The experiments also showed that the activity of protein kinases B (Akt)-mTOR axis was inhibited by VES. VES-induced AMPK activation could be attenuated by Akt activation. Overall, our studies demonstrated that AMPK was involved in the VES-induced autophagy. Crosstalk exists between AMPK and the Akt/mTOR axis. The results elucidated the mechanism of VES-induced autophagy in human gastric cancer cells.
authors: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, China.
authors: Yang
authors: Y
authors: Yu
authors: School of Public Health, North China University of Science and Technology, Tangshan, China.
authors: Liying
authors: L
authors: Hou
authors: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, China.
authors: Huacui
authors: H
authors: Song
authors: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, China.
authors: Peixiang
authors: P
authors: Xu
authors: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, China.
authors: Yue
authors: Y
authors: Sun
authors: Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, China. wukun_15000@126.com.
authors: Kun
authors: K
authors: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D014810:Vitamin E; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Akt; Autophagy; Gastric cancer cells; Vitamin E succinate; mTOR