Abstract：
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.
摘要：
癌细胞需要更多的葡萄糖供应，主要是由于它们的有氧糖酵解，被称为Warburg效应。葡萄糖转运蛋白1（GLUT1）的葡萄糖转运是葡萄糖摄取的限速步骤，使其成为潜在的癌症治疗靶点。然而,GLUT1广泛表达并在多种细胞中执行关键功能，其不加区分的抑制作用会引起严重的副作用。在这项研究中,我们设计并合成了一种光老化的GLUT1抑制剂WZB117-PPG,以时空可控的方式抑制癌细胞的生长.WZB117-PPG在可见光照射下对癌细胞表现出显著的光解效率和显著的细胞毒性，副作用最小。确保其作为潜在癌症治疗的安全性。此外，我们的定量蛋白质组学数据描绘了葡萄糖剥夺下癌细胞反应的全面肖像，强调细胞通过坏死而不是凋亡死亡的机制。我们认为我们的研究提供了一种潜在可靠的癌症治疗策略，并且可以用作研究营养剥夺相关应激反应的时空可控触发因素。
