title: The wedelolactone derivative inhibits estrogen receptor-mediated breast, endometrial, and ovarian cancer cells growth.
abstract: Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers. Attenuating ER activities by natural products and their derivatives is a relatively practical strategy to control and reduce breast, endometrial, and ovarian cancer risk. Here, we found 3-butoxy-1,8,9-trihydroxy-6H-benzofuro[3,2-c]benzopyran-6-one (BTB), a new derivative of wedelolactone, could effectively inhibit the 17-estradiol (E2)-induced ER transactivation and suppress the growth of breast cancer as well as endometrial and ovarian cancer cells. Our results indicate that 2.5 μM BTB effectively suppresses ER-positive, but not ER-negative, breast, endometrial, and ovarian cancer cells. Furthermore, our data indicate that BTB can modulate ER transactivation and suppress the expression of E2-mediated ER target genes (Cyclin D1, E2F1, and TERT) in the ER-positive MCF-7, Ishikawa, and SKOV-3 cells. Importantly, this BTB mediated inhibition of ER activity is selective since BTB does not suppress the activities of other nuclear receptors, including glucocorticoid receptor and progesterone receptor, suggesting that BTB functions as a selective ER signaling inhibitor with the potential to treat breast, endometrial, and ovarian cancers.
authors.affiliation: School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, China ; George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Defeng
authors.initials: D
authors.lastname: Xu
authors.affiliation: George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Lin
authors.affiliation: George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Chiuan-Ren
authors.identifier: 0000-0002-9825-2008
authors.initials: CR
authors.lastname: Yeh
authors.affiliation: George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Max A
authors.initials: MA
authors.lastname: Cheng
authors.affiliation: Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan.
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Chen
authors.affiliation: George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA ; Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
authors.affiliation: George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003374:Coumarins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C051122:wedelolactone; D019938:Cyclin D1; D004958:Estradiol