Ergosterol is a sterol unique to fungal cell membranes with antioxidant and antiproliferative activities. Ergosterol activates mitochondrial ACSL1 to promote fatty acid β-oxidation, thereby alleviating fatty liver and insulin resistance, while reducing inflammation through inhibition of the NF-κB pathway. Ergosterol can be used in research related to metabolic diseases and antifungal drugs[1-4].
In vitro, Ergosterol (2.5–40μM) was applied to human breast cancer cells MCF-7 and MDA-MB-231 for 24–96h. Ergosterol inhibited cell viability, induced G0/G1 phase cell cycle arrest, suppressed spheroid formation, downregulated c-Myc and cyclin D1 expression, blocked β-catenin nuclear translocation, inhibited AKT and GSK-3β phosphorylation, promoted β-catenin degradation, suppressed protein synthesis, and downregulated USP47 and USP9x expression[5]. Ergosterol (0–300μM) was applied to MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7 human breast cancer cells and 4T1 mouse breast cancer cells for 24–48h. Ergosterol dose-dependently inhibited the viability, migration, and invasion of breast cancer cells, reduced colony number and size, induced apoptosis in MDA-MB-231 cells, and upregulated the mRNA and protein expression of Foxo3 and its downstream targets BimL, BimS, Fas, and FasL[6].
In vivo, Ergosterol (50mg/kg and 100mg/kg) was administered once daily by oral gavage to Streptozotocin (STZ)-induced diabetic nephropathy mice and normal mice for 5 weeks. Ergosterol reduced fasting blood glucose and blood lipids, elevated serum insulin levels and HOMA-β, alleviated kidney injury, and downregulated the mRNA and protein expression of IL-6, TNF-α, and MCP-1 in serum and renal tissue, while inhibiting p-NF-κB(p65), COX-2, and iNOS expression in renal tissue[7]. Ergosterol (0, 2, 7mg/kg) was incorporated into the diet and fed daily to wild-type C57BL/6NCrl male mice for 6 weeks. Ergosterol (7mg/kg) increased vitamin D3 levels in serum, liver, and kidney[8].
References:
[1] Yao M, Li C, Dang M, et al. Ergosterol: Biological Activities, Mechanistic Evidence, Pharmacokinetic Barriers, and Delivery Strategies. Int J Mol Sci. 2026 May 8;27(10):4198.
[2] Stefaniak-Skorupa J, Milewska MJ. Ergosterol and Lanosterol Derivatives: Synthesis and Possible Biomedical Applications. ChemMedChem. 2025 May 19;20(10):e202400948.
[3] Jordá T, Puig S. Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae. Genes (Basel). 2020 Jul 15;11(7):795.
[4] Suárez Y, Fernández C, Ledo B, et al. Differential effects of ergosterol and cholesterol on Cdk1 activation and SRE-driven transcription. Eur J Biochem. 2002 Mar;269(6):1761-71.
[5] Li X, Wu Q, Xie Y, et al. Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors. Oncotarget. 2015 Jul 10;6(19):17832-46.
[6] Nilkhet S, Vongthip W, Lertpatipanpong P, et al. Ergosterol inhibits the proliferation of breast cancer cells by suppressing AKT/GSK-3beta/beta-catenin pathway. Sci Rep. 2024 Aug 24;14(1):19664.
[7] Liu C, Zhao S, Zhu C, et al. Ergosterol ameliorates renal inflammatory responses in mice model of diabetic nephropathy. Biomed Pharmacother. 2020 Aug;128:110252.
[8] Zheng ZG, Zhang YP, Zhang XY, et al. Ergosterol alleviates hepatic steatosis and insulin resistance via promoting fatty acid β-oxidation by activating mitochondrial ACSL1. Cell Rep. 2025 Jan 28;44(1):115203.