“Colon adenocarcinoma (COAD) is characterized by the metabolic reprogramming, such as the Warburg effect, which drives tumor progression and immunosuppression. Hypoxia-inducible factor 1 (HIF-1) 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-1agonist DMOG partially reversed cannabidiol’s antiglycolytic and antitumor effects, and thus confirmed pathway dependency. Synergy with the glycolysis inhibitor 2-DG enhanced therapeutic efficacy, which highlighted cannabidiol’s potential to overcome metabolic resistance.
These findings establish cannabidiol as a novel inhibitor of HIF-1/LDHA-driven glycolysis, and thus provide a translational strategy for metabolic vulnerability in COAD.”
https://pubmed.ncbi.nlm.nih.gov/41219135/
https://www.worldscientific.com/doi/10.1142/S0192415X25500958
“The phrase “Cannabidiol Reprograms Glucose Metabolism in Colorectal Adenocarcinoma by Targeting HIF-1α/LDHA Pathway” means that cannabidiol (CBD) helps fight colon cancer cells by altering how they use glucose (sugar) for energy, specifically by interfering with a key biological pathway involving the proteins HIF-1α and LDHA.”
“In summary, the study found that CBD acts as a novel inhibitor of the HIF-1α/LDHA pathway, suppressing the abnormal glucose metabolism essential for colorectal cancer growth and providing a potential therapeutic strategy for treatment.”