ArticleFrontiers in pharmacology2026
Brusatol suppresses meningioma progression via targeting HMGCR to restrict the cholesterol biosynthesis and inhibit PI3K/AKT signaling pathway.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol metabolism, remains underexplored in meningioma. Additionally, the therapeutic potential of Brusatol (Bru), a triterpene lactone compound with anticancer properties, has yet to be systematically evaluated. This research investigates Bru's efficacy in meningioma treatment and HMGCR-related mechanisms. Methods: IC Results: Bru inhibited the proliferation, migration, and invasion of meningioma cells, induced apoptosis, and reduced cholesterol accumulation. Proteomic, transcriptomic, and bioinformatic analyses, along with molecular docking, revealed that Bru targeted HMGCR to restrict cholesterol biosynthesis and inhibit the PI3K/AKT signalling pathway. These findings were validated through a series of experiments, including surface plasmon resonance assay, HMGCR knockdown and overexpression, and rescue experiments where HMGCR knockdown or Bru treatment was reversed with an Akt activator SC79. Conclusion: These findings demonstrate that Brusatol suppresses meningioma progression by inhibiting of HMGCR and the PI3K/AKT signaling pathway.
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