Targeting tumor metabolism: The dual attack of emodin on glycolysis and oxidative phosphorylation in esophageal squamous cell carcinoma

作者：Xin Su, Wanyu Yang, Zhiqiang Yan, Zhihua Hao, Jing Jin, Yanyu Liu, Siqi Wu, Yutong He · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156958 · 被引用次数：8 · 研究领域：Phytochemistry and biological activity of medicinal plants、Aldose Reductase and Taurine、Natural Compound Pharmacology Studies

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) exhibits elevated death rate and varying resistance to multiple chemotherapeutic agents. Emodin, a key constituent of rhubarb, has demonstrated anticancer activities in colorectal and breast cancers. However, its application and mechanism in ESCC await full clarification. PURPOSE: This study investigates emodin's inhibitory impacts on ESCC in vitro and in vivo and explores its underlying molecular mechanisms, with the aim of identifying a potential candidate for ESCC treatment. METHODS: To explore the mechanisms by which emodin acts in ESCC, network pharmacology, bioinformatics analysis, proteomic profiling, and Seahorse assays were employed to assess alterations in cellular energy metabolism. The expression extent of the end result markers and pathway proteins induced by emodin were assessed using Western blotting. To evaluate the potential toxicity and antitumor efficacy of emodin in ESCC, a xenograft tumor model was utilized in vivo. RESULTS: Emodin inhibited ESCC cell proliferation, facilitated intrinsic apoptosis, and induced G2/M phase arrest. Proteomic analysis results showed that emodin disrupted cellular energy metabolism by inhibiting both mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. Network pharmacology and rescue experiments identified the p53 and FOXO signaling pathways as key mediators of these effects. In vivo xenograft experiments further supported the inhibitory activity of emodin in ES...