title: Subglutinol A, an immunosuppressive α-pyrone diterpenoid from Fusarium subglutinans, acts as an estrogen receptor antagonist.
abstract: Subglutinol A is an immunosuppressive α-pyrone diterpenoid isolated from Fusarium subglutinans that exhibits osteogenic activity. Several non-steroid mycotoxins isolated from various strains of Fusarium fungi exhibit female steroid hormone activities. In this study, we characterized the estrogenic activity of subglutinol A (1). Subglutinol A blocked the 17β-estradiol-induced activation of reporter plasmids and endogenous estrogen-responsive target genes in a dose-dependent manner and efficiently destabilized ER proteins as shown using the estrogen receptor antagonist ICI 182,780. Subglutinol A also displaced the specific binding of [(3)H]17β-estradiol from ER in MCF-7 whole-cell ligand binding assays. These data demonstrate the potential of subglutinol A as an ER antagonist though its competition with 17β-estradiol for direct ER association.
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea; Department of Sports Medicine, College of Health Science, Cheongju University, Chungbuk, Republic of Korea.
authors.forename: Wonchung
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea.
authors.forename: Joonwoo
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, Chungbuk National University, Chungbuk, Republic of Korea.
authors.forename: Yong Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Duke University, Durham, NC 27708, United States; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, United States. Electronic address: jiyong.hong@duke.edu.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Kwangjingu, Kunjadong, Seoul 143-747, Republic of Korea. Electronic address: yjlee@sejong.ac.kr.
authors.forename: YoungJoo
authors.initials: Y
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004224:Diterpenes / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D061986:MCF-7 Cells; D011753:Pyrones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004224:Diterpenes; D047628:Estrogen Receptor alpha; D007166:Immunosuppressive Agents; D011753:Pyrones; C551806:subglutinol A
keywords: Antiestrogen; Estrogen receptor; Subglutinol