title: Plant 2-arylobenzofurans demonstrate a selective estrogen receptor modulator profile.
abstract: We have isolated from the plant Onobrychis ebenoides three novel arylobenzofurans with binding affinity for the estrogen receptor. In this study, we evaluated these arylobenzofurans, namely ebenfuran I, ebenfuran II and ebenfuran III for their potential selective estrogen receptor modulator (SERM)-like properties. We examined their ability, (1) to induce the insulin growth factor binding protein-3 (IGFBP-3) in MCF-7 breast cancer cells, (2) to stimulate differentiation and mineralization of osteoblastic cell culture by histochemical staining for alkaline phosphatase, Alizarin Red-S staining and calcium levels in the supernatants and (3) to inhibit cell proliferation of cervical adenocarcinoma (Hela) cells by use of the MTT assay. An estrogen receptor mediated effect was investigated by carrying out chloramphenicol acetyl transferase (CAT) assay on transient MCF-7 transfectants. Estradiol and the "pure" antiestrogen ICI 182780 were included to serve as control samples of the estrogenic and antiestrogenic effect respectively. Our data reveal that ebenfuran II is a highly potent SERM, exhibiting antiestrogenic activity in breast cancer cells via the estrogen receptor, estrogenic effect on osteoblasts and no stimulatory effect on cervix adenocarcinoma cells. In conclusion, our study is the first to demonstrate that plant derived arylobenzofurans show a SERM profile and may be considered for the prevention and treatment of diseases such as breast cancer, cervical cancer and osteoporosis.
authors.affiliation: Laboratory of Biological Chemistry, Department of Biological Chemistry, Medical School, National University of Athens, 75 M. Asias Str., Goudi, GR-115 27 Athens, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Papoutsi
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papaevangeliou
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Zoumpourlis
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.forename: Sofia
authors.initials: S
authors.lastname: Mitakou
authors.forename: Anastasios
authors.initials: A
authors.lastname: Kalofoutis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D005663:Furans / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D010946:Plants, Medicinal; D011960:Receptors, Estrogen / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000880:Anthraquinones; D001572:Benzofurans; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D005663:Furans; D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077267:Fulvestrant; C004468:Alizarin Red S; D004958:Estradiol; D015500:Chloramphenicol O-Acetyltransferase; D000469:Alkaline Phosphatase; C022616:thiazolyl blue; D002118:Calcium