Characterization of Chlorogenic Acid as a Two-Photon Fluorogenic Probe that Regulates Glycolysis in Tumor Cells under Hypoxia

作者：Qinghua Wang, Qingyang Zhang, Zhihui Zhang, Ming Ji, Tingting Du, Jing Jin, Jian‐Dong Jiang, Xiaoguang Chen, Hai‐Yu Hu · 发表于：Journal of Medicinal Chemistry · 年份：2023 · DOI：10.1021/acs.jmedchem.2c01317 · 被引用次数：14 · 研究领域：Cancer, Hypoxia, and Metabolism、Nanoplatforms for cancer theranostics、Retinoids in leukemia and cellular processes

High levels of steady-state mitochondrial reactive oxygen species (ROS) and glycolysis are hallmarks of cancer. An improved understanding of interactions between tumor energetics and mitochondrial ROS modulation is useful for the development of new anticancer strategies. Here, we show that the natural product chlorogenic acid ( CGA ) specifically scavenged abnormally elevated mitochondrial O 2 •– and exhibited a two-photon fluorescence turn-on response to tumor cells under hypoxia and tumor tissues in vivo . Furthermore, we illustrated that CGA treatment reduced O 2 •– levels in cells, hampered activation of AMP-activated protein kinase (AMPK), and shifted metabolism from glycolysis to oxidative phosphorylation (OXPHOS), resulting in inhibition of tumor growth under hypoxia. This study demonstrates an efficient two-photon fluorescent tool for real-time assessment of mitochondrial O 2 •– and a clear link between reducing intracellular ROS levels by CGA treatments and regulating metabolism, as well as undeniably helpful insights for the development of new anticancer strategies.