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

作者：Hongen Geng, Lin‐Feng Chen, ShuWen Lv, Mengzhao Li, Xiaoping Huang, Man Li, Changlin Liu, Changlin Liu, Chunrong Liu, Chunrong Liu · 发表于：Journal of Proteome Research · 年份：2024 · DOI：10.1021/acs.jproteome.3c00469 · 被引用次数：7 · 研究领域：Cancer, Hypoxia, and Metabolism、Nanoplatforms for cancer theranostics、Retinoids in leukemia and cellular processes

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.