%0 Journal Article
%T Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research.
%A Geng H
%A Chen L
%A Lv S
%A Li M
%A Huang X
%A Li M
%A Liu C
%A Liu C
%J J Proteome Res
%V 23
%N 2
%D 2024 02 2
%M 38170682
%F 5.37
%R 10.1021/acs.jproteome.3c00469
%X Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the rate-limiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.