Coumestrol is a natural, orally active coumestan phytoestrogen. Coumestrol competitively binds estrogen receptor ERα (IC50=11nM) and ERβ (IC50=2nM) to regulate estrogen-responsive genes. Coumestrol inhibits aromatase and 17β-hydroxysteroid dehydrogenase and weakly antagonizes pregnane X receptor to reduce xenobiotic-metabolizing enzyme expression. Coumestrol is used for breast cancer, endometrial cancer, osteoporosis, and postmenopausal metabolic disorder research[1-4].
In vitro, 143B and HOS osteosarcoma cells were treated with 0-100μM Coumestrol for 24h. Coumestrol reduced cell viability and proliferation, promoted apoptosis, increased G1-phase cell proportion, decreased S-phase cell proportion, and inhibited migration and invasion[5]. ES2 human epithelial ovarian cancer cells were treated with 0-100μM Coumestrol for 1-4 days. Coumestrol inhibited cell proliferation and invasion[6]. HCT116, HT-29, and A549 cells were treated with 80μM Coumestrol for 3-14h. Coumestrol reduced cell viability and colony formation[7].
In vivo, pregnant ICR mice received oral gavage of 200μg/kg Coumestrol once daily for 11 doses starting at 6.5 days post-coitum. Coumestrol decreased duodenal and jejunal alkaline phosphatase activity and reduced IAP, c-fos, and VEGF mRNA expression[8]. High-fat diet-fed ovariectomized C57BL/6J mice received subcutaneous injection of 5mg/kg Coumestrol once daily for 10 weeks. Coumestrol prevented adipose tissue accumulation and reduced hepatic lipid accumulation[9]. Cardiac dysfunction model C57BL/6 mice received oral gavage of 5mg/kg/day Coumestrol once daily for 2 weeks. Coumestrol reduced cardiac oxidative damage, cardiomyocyte apoptosis, and cardiac dysfunction, and decreased serum cTnT, CK-MB, and LDH levels[10].
References:[1] Sun JS, Li YY, Liu MH, et al. Effects of coumestrol on neonatal and adult mice osteoblasts activities. J Biomed Mater Res A. 2007 Apr;81(1):214-23.
[2] Wang T, Wang Y, Zhuang X, et al. Interaction of Coumarin Phytoestrogens with ERα and ERβ: A Molecular Dynamics Simulation Study. Molecules. 2020 Mar 5;25(5):1165.
[3] Whitten PL, Patisaul HB, Young LJ. Neurobehavioral actions of coumestrol and related isoflavonoids in rodents. Neurotoxicol Teratol. 2002 Jan-Feb;24(1):47-54.
[4] Burroughs CD. Long-term reproductive tract alterations in female mice treated neonatally with coumestrol. Proc Soc Exp Biol Med. 1995 Jan;208(1):78-81.
[5] Haiqing W, Yangli J, Feng Z. DExD-box helicase 39 A, targeted by coumestrol, facilitates the malignant behaviors of osteosarcoma cells. Hereditas. 2025 Oct 28;162:218.
[6] Lim W, Jeong W, Song G. Coumestrol suppresses proliferation of ES2 human epithelial ovarian cancer cells. J Endocrinol. 2016 Feb;228(3):149-160.
[7] Kim J, Lee S, Jang M, et al. Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a Natural Haspin Kinase Inhibitor. Int J Mol Sci. 2017 Oct;18(10):2228.
[8] Kirihata Y, Horiguchi Y, Ueda M, et al. Effects of coumestrol administration to pregnant and lactating mice on intestinal alkaline phosphatase activity. Reprod Dev. 2010;56(5):645-654.
[9] Park S, Sim KS, Heo W, et al. Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice. Nutrients. 2023 Feb;15(4):954.
[10] Wu ZZ, Rao M, Xu S, et al. Coumestrol ameliorates doxorubicin-induced cardiotoxicity via activating AMPKα. Free Radical Res. 2020;54(11):882-897.