title: Cancer-specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells.
abstract: The metabolic phenotype of cancer is considered an ideal target for anticancer therapy. In ovarian cancer, glucose transporter 1 (GLUT1) is overexpressed and positron emission tomography (PET) using [18(F)] fluorodeoxyglucose (FDG), as a metabolic tumor parameter, has been found to be an effective diagnostic tool. In this study, we have characterized the selective cytotoxicity of resveratrol (RSV) in ovarian cancer cells through glucose metabolism regulation via GLUT1 modulation. We have demonstrated that, in contrast to primary normal ovarian epithelial cells, RSV selectively inhibited glucose uptake and induced apoptosis irrespective of p53 status in vitro. RSV had no affect on GLUT1 mRNA and protein expressions but interrupted intracellular GLUT1 trafficking to the plasma membrane. Suppressed plasma membrane GLUT1 localization in ovarian cancer was found to be associated with the inhibition of Akt activity by RSV, as confirmed by the action of the Akt inhibitors (LY294002 and Akt inhibitor IV), as well as overexpression of a constitutive active form of Akt. Taken together, these findings suggested that RSV induced apoptosis in ovarian cancer cells by impairing glucose uptake, a process involving Akt-regulated plasma membrane GLUT1 trafficking.
authors.affiliation: Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: HyeRan
authors.initials: H
authors.lastname: Gwak
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.affiliation: Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.|Departments of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada.|Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Departments of Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.|Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
authors.affiliation: Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D000077185:Resveratrol
keywords: Akt; GLUT1; glucose metabolism; ovarian cancer; resveratrol