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: HyeRan Gwak, Guy Haegeman, Benjamin K Tsang, Yong Sang Song
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 54 Issue 12 Pg. 1529-40 (Dec 2015) ISSN: 1098-2744 [Electronic] United States
• PMID: 25307508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Glucose Transporter Type 1
• RNA, Messenger
• SLC2A1 protein, human
• Stilbenes
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins c-akt
• Glucose
• Resveratrol

Topics

• Apoptosis (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Membrane (drug effects, metabolism)
• Epithelial Cells (drug effects, metabolism)
• Female
• Glucose (metabolism)
• Glucose Transporter Type 1 (antagonists & inhibitors)
• Humans
• Ovarian Neoplasms (drug therapy, metabolism)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors)
• RNA, Messenger (genetics)
• Resveratrol
• Signal Transduction (drug effects)
• Stilbenes (pharmacology)
• Tumor Suppressor Protein p53 (metabolism)