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.

SlHSP17.7 Ameliorates Chilling Stress-Induced Damage by Regulating Phosphatidylglycerol Metabolism and Calcium Signal in Tomato Plants.

Tomatoes (Solanum lycopersicum L.) are sensitive to chilling temperatures between 0 °C and 12 °C owing to their tropical origin. SlHSP17.7, a cytoplasmic heat shock protein, interacts with cation/calcium exchanger 1-like (SlCCX1-like) protein and promotes chilling tolerance in tomato fruits (Zhang, et al., Plant Sci., 2020, 298, 1-12). The overexpression of SlHSP17.7 can also promote cold tolerance in tomato plants, but its specific mechanism remains unclear. In this study, we show that the overexpression of SlHSP17.7 in tomato plants enhances chilling tolerance with better activity of photosystem II (PSII). Metabolic analyses revealed that SlHSP17.7 improved membrane fluidity by raising the levels of polyunsaturated fatty acids. Transcriptome analyses showed that SlHSP17.7 activated Ca2+ signaling and induced the expression of C-repeat binding factor (CBF) genes, which in turn inhibited the production of reactive oxygen species (ROS). The gene coexpression network analysis showed that SlHSP17.7 is coexpressed with SlMED26b. SlMED26b silencing significantly lowered OE-HSP17.7 plants' chilling tolerance. Thus, SlHSP17.7 modulates tolerance to chilling via both membrane fluidity and Ca2+-mediated CBF pathway in tomato plants.