Title
Imatinib mesylate inhibits glucose uptake in gastrointestinal stromal tumor cells by downregulation of the glucose transporters recruitment to the plasma membrane Imatinib mesylate inhibits glucose uptake in gastrointestinal stromal tumor cells by downregulation of the glucose transporters recruitment to the plasma membrane
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
,
Subject
Human medicine
Source (journal)
American journal of biochemistry and biotechnology. - Place of publication unknown
Volume/pages
1(2005) :2 , p. 95-102
ISSN
1553-3468
Carrier
E
Target language
English (eng)
Abstract
Imatinib mesylate, the inhibitor of the KIT protein tyrosine kinase that is constitutively activated in Gastrointestinal Stromal Tumors (GISTs), has been established as the first highly effective drug in the treatment of patients with advanced GISTs. Recent studies suggest that changes in the glucose metabolism could be an additional mechanism of the anti-proliferative action of imatinib. The aim of this study was to investigate the effect on glucose flux and metabolism in a human GIST882 cell line after exposure to imatinib. Imatinib induced a concentration-dependent inhibition of cell proliferation in GIST882 cells (IC50, 0.030 ± 0.006 µM). By 18 F-FDG uptake measurements, after 24 h exposure to the drug at concentrations of 0.03 µM and 0.3 µM, the glucose uptake decreased by ~25% and ~95%, respectively. Moreover, after a 3-h treatment at the concentration of 0.3 µM of imatinib the decrease in glucose-uptake was already more than 50%. After 24-h of treatment with 0.3 µM imatinib, the measurements of the hexokinase and glucose-6-phosphate dehydrogenase activity revealed a 30% and 37% decrease, respectively. Western blotting disclosed mainly expression of glucose transporter GLUT-2 in GIST cells. Exposure of GIST cells to imatinib resulted in the decline of the GLUT-2 receptor recruitment to cell membrane, which paralleled with the elevated amount of the total KIT protein. These findings suggest that a rapid decline in glucose uptake following imatinib treatment in GIST cells is dependent on glucose transporter impaired anchorage to the plasma membrane, with the subsequent recruitment of KIT protein.