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Med."],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Colon adenocarcinoma (COAD) is characterized by the metabolic reprogramming, such as the Warburg effect, which drives tumor progression and immunosuppression. Hypoxia-inducible factor 1[Formula: see text] (HIF-1[Formula: see text] and lactate dehydrogenase A (LDHA) are critical regulators of this metabolic shift, but existing therapies are insufficiently specific to it. This study investigates the antitumor mechanisms of cannabidiol, a non-psychoactive phytocannabinoid, by using integrative multi-omics and functional validation. Single-cell transcriptomics revealed that cannabidiol reduced tumor cell proportions and suppressed glycolytic activity in COAD. Network pharmacology identified PTGS2 as a central target, with proteomic data confirming its overexpression in COAD tissues and association with poor prognosis. In vitro, cannabidiol inhibited COAD cell proliferation, migration, and colony formation while downregulating HIF-1[Formula: see text], LDHA, and GLUT1 expression. Metabolic assays demonstrated associated dose-dependent reductions in ATP production, glucose uptake, and lactate levels. Rescue experiments using the HIF-1[Formula: see text] agonist DMOG partially reversed cannabidiol\u2019s antiglycolytic and antitumor effects, and thus confirmed pathway dependency. Synergy with the glycolysis inhibitor 2-DG enhanced therapeutic efficacy, which highlighted cannabidiol\u2019s potential to overcome metabolic resistance. These findings establish cannabidiol as a novel inhibitor of HIF-1[Formula: see text]\/LDHA-driven glycolysis, and thus provide a translational strategy for metabolic vulnerability in COAD.<\/jats:p>","DOI":"10.1142\/s0192415x25500958","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:11:23Z","timestamp":1762917083000},"page":"2561-2578","source":"Crossref","is-referenced-by-count":4,"title":["Cannabidiol Reprograms Glucose Metabolism in Colorectal Adenocarcinoma by Targeting HIF-1\u03b1\/LDHA Pathway"],"prefix":"10.1142","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-5811","authenticated-orcid":false,"given":"Yuzhe","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 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