Therapeutic opportunities offered by tumor metabolism: GLUT1 inhibition

Most of cancers originating from various tissues show an overexpression of glucose transporters (GLUTs), in particular of GLUT1. This is due to the fact that cancer cells require enhanced glucose supply to support their less efficient energy production through anaerobic glycolysis (Warburg effect). Nowadays, GLUT1 is being considered as a promising target for anticancer therapies, although only a few selective inhibitors have been so far reported [1]. We have identified some efficient GLUT1 inhibitors among a series of oxime derivatives, and we have constructed an in silico GLUT1 model which was used to predict the binding poses and the most significant interactions that these compounds establish with GLUT1 [2], as well as to support the molecular design of more potent inhibitors [3]. Some of these compounds proved to efficiently inhibit glucose uptake and cell proliferation of a lung cancer cell line. We were also able to visualize and quantify the inhibition of glucose uptake in lung cancer cells by fluorescence microscopy. To this end, we used a fluorescent D-glucose analogue, 2-NBDG, which is an established probe for the detection of glucose taken up by cultured cells.