Plant-derived estrogenic compounds, known as phytoestrogens, have drawn attention due to their potential therapeutic use. From epidemiologic data, Asian people, who frequently consume phytoestrogen-rich diets such as soybean, have been found to have a lower rate of osteoporotic fractures, cardiovascular diseases, postmenopausal symptoms (PMS), and certain cancers than Western populations.1) These health advantages are notably decreased when Asians adopt a Western lifestyle and eating habits. In other studies, phytoestrogens have been thought to show beneficial effects in cardiovascular and Alzheimer treatments. [2][3][4][5] Research involving phytoestrogens found largely in legumes, seeds, fruits, and vegetables has been extensively conducted. [6][7][8][9] Red clover, the first plant known for its estrogenic activities, contains high amounts of formononetin and biochanin A. 10) Both compounds were found to interact with estrogen receptors (ERs) due to their structural similarity to 17b-estradiol.11) Currently, there are four groups of phenolic compounds classified as phytoestrogens: isoflavones, stilbenes, coumestans, and lignans.11) Based on current findings revealing several new phytoestrogen candidates, it is believed that other, yet unknown compounds might possess estrogen-like activities with beneficial therapeutic potential. [12][13][14] Sesquiterpenoid xanthorrhizol, a major bioactive compound isolated from Curcuma xanthorrhiza ROXB. commonly known as Javanese turmeric, has often been cited for its great potential in food and medical applications. Xanthorrhizol has been shown to exert antioxidant, 15,16) anti-inflammatory, 16,17) antibacterial, 18) neuroprotective, 19) nephroprotective, 20) and hepatoprotective activity. 21,22) Furthermore, xanthorrhizol has been shown to have efficacy as a tumor chemopreventive agent. Xanthorrhizol was shown to suppress 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated tumor promotion in mouse skin cells 22) and attenuate lung metastasis in an in vivo model. 23) In HeLa cervical cancer cells, p53 and bax-dependent apoptosis were stimulated with xanthorrhizol treatment 24) while in MCF-7 breast cancer cells apoptosis was modulated through bcl-2, p53, and poly(ADP-ribose)polymerase-1 (PARP-1). 25) In another study using HepG2 hepatoma cells, xanthorrhizol induced the cells to undergo apoptosis via the mitochondrial pathway.26) In addition, it has been reported that the combination of xanthorrhizol and curcumin promoted apoptosis in MDA-MB-231 breast cancer cells.
27)In the present study, using the Gal4/ERs ligand-binding transactivation assay, we examined whether xanthorrhizol might possess an estrogenic activity. It was hoped that this assay would provide further information regarding xanthorrhizol and its benefit as a phytoestrogen. The assay was conducted in transiently-transfected ER-negative COS-7 cells using both subtypes of ERs, ERa and ERb, and ligand binding domains (LBD). To determine if xanthorrhizol could induce endogenous ER-estrogen response element (ERE)...