葡萄糖转运蛋白
过剩1
癌细胞
瓦博格效应
癌症
葡萄糖摄取
细胞凋亡
运输机
糖酵解
癌症研究
化学
细胞生物学
生物化学
生物
新陈代谢
内科学
医学
内分泌学
胰岛素
基因
作者
Hongen Geng,Linfeng Chen,Shu‐Hui Lv,Mengzhao Li,Xiaoping Huang,Man Li,Changlin Liu,Chunrong Liu
标识
DOI:10.1021/acs.jproteome.3c00469
摘要
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.
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