Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research

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.

GLUT1 inhibitor; TMT; Warburg effect; cancer suppression; glucose deprivation; photocage; quantitative proteomics.