title: Estrogenic Activity of Hyperforin in MCF-7 Human Breast Cancer Cells Transfected with Estrogen Receptor.
abstract: Hyperforin, a major active compound of St. John's wort extract, affects estrogenic activity. In this study, the compound evoked estrogen response element-dependent luciferase activity and cell proliferation in MCF-7 cells. Hyperforin-induced cell proliferation was significantly inhibited by the estrogen receptor antagonist ICI 182,780. These results suggested that hyperforin had estrogenic and cell proliferation activities, which were stimulated via the estrogen receptor. Compared to 17β-estradiol, hyperforin showed significantly lower estrogenic activity and cell proliferation. The mechanism underlying the estrogenic activity of hyperforin was unknown, therefore, in this study, for the first time, the expression and post-translational modification of proteins were determined and compared among control, 17β-estradiol-treated, and hyperforin-treated cells using proteomic techniques. A total of 453 proteins were identified, of which 282 proteins were significantly modulated in hyperforin-treated cells compared to 17β-estradiol-treated cells. Ingenuity pathway analysis also demonstrated that hyperforin treatment induced less cell proliferation than 17β-estradiol by downregulating estrogen receptor 1. Protein network analysis showed that cell proliferation was regulated mainly by cyclin D1 and extracellular signal-regulated kinases. In conclusion, although, hyperforin exhibited lower estrogenic activity than 17β-estradiol, the compound induced lower levels of cancer cell proliferationin vitro.
authors.affiliation: Korea Basic Science Institute, Daejeon, Republic of Korea.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Technology and BK21 Plus Program, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Kyung Seo
authors.initials: KS
authors.lastname: Oh
authors.affiliation: Department of Food Science and Technology and BK21 Plus Program, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Jeonnam Biofood Technology Center, Naju, Republic of Korea.
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Bang
authors.affiliation: Department of Food Science and Technology and BK21 Plus Program, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Hwan Seon
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Food Science and Technology and BK21 Plus Program, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Bipin
authors.initials: B
authors.lastname: Vaidya
authors.affiliation: Department of Food Science and Technology and BK21 Plus Program, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Duwoon
authors.initials: D
authors.lastname: Kim
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000032:analysis*; D006801:Humans; D061986:MCF-7 Cells; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D020543:Proteome; D020218:Response Elements; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology; D014162:Transfection
chemical_list: D004967:Estrogens; D020543:Proteome; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin