The glucose transporter GLUT1 is frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely primarily on glycolysis, a low-efficiency metabolic pathway that necessitates a very high rate of glucose consumption. Because blocking GLUT1 is a promising anticancer strategy, we developed a novel class of GLUT1 inhibitors based on the 4-aryl-substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a notable antiproliferative effect. In contrast to their 5-aryl-substituted regioisomers, the newly synthesized compounds reported herein do not display significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analogue of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small molecules, or by further optimized derivatives, may be a successful approach in the development of novel anticancer drugs.

Salicylketoximes that target glucose transporter 1 restrict energy supply to lung cancer cells

GRANCHI, CARLOTTA;PATERNI, ILARIA;TUCCINARDI, TIZIANO;MINUTOLO, FILIPPO
2015-01-01

Abstract

The glucose transporter GLUT1 is frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely primarily on glycolysis, a low-efficiency metabolic pathway that necessitates a very high rate of glucose consumption. Because blocking GLUT1 is a promising anticancer strategy, we developed a novel class of GLUT1 inhibitors based on the 4-aryl-substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a notable antiproliferative effect. In contrast to their 5-aryl-substituted regioisomers, the newly synthesized compounds reported herein do not display significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analogue of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small molecules, or by further optimized derivatives, may be a successful approach in the development of novel anticancer drugs.
Granchi, Carlotta; Qian, Yanrong; Lee, Hyang Yeon; Paterni, Ilaria; Pasero, Carolina; Iegre, Jessica; Carlson, Kathryn E; Tuccinardi, Tiziano; Chen, Xiaozhuo; Katzenellenbogen, John A; Hergenrother, Paul J; Minutolo, Filippo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/758268
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