title: Brefeldin A is an estrogenic, Erk1/2-activating component in the extract of Agaricus blazei mycelia.
abstract: We purified an Erk1/2-activating component in Agaricus blazei and identified it as brefeldin A (BFA). The extract of A. blazei mycelia (ABE) previously showed an estrogenic gene-expression profile and positive effects in patients with cardiovascular symptoms. Here, we demonstrate that BFA has estrogenic activity in reporter gene assays and stimulates an estrogen-receptor pathway revealed by activation of Erk1/2, although BFA had no growth-stimulating activity in breast cancer MCF-7 cells. The presence of estrogenic activity without any explicit growth-stimulating effect is unique to BFA, and such components are termed here "silent estrogens". To test this hypothesis, we examined the target-gene transcription and signaling pathways induced by BFA. Furthermore, BFA was found in the mycelium but not fruiting body of A. blazei, suggesting the potential use of ABE for therapeutics and its supplementary use in traditional medicines and functional foods.
authors.affiliation: Biomedical Research Institute, Research and Innovation Promotion Headquarters, National Institute of Advanced Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Furutani
authors.forename: Sadao
authors.initials: S
authors.lastname: Kimura
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kawabata
authors.forename: Michiko
authors.initials: M
authors.lastname: Furutani
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tomoh
authors.initials: T
authors.lastname: Masaki
authors.forename: Rumiko
authors.initials: R
authors.lastname: Matsuoka
authors.forename: Ryoiti
authors.initials: R
authors.lastname: Kiyama
mesh_terms: D000364:Agaricus / Q000737:chemistry / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004967:Estrogens / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017931:DNA Primers; D004967:Estrogens; D020126:Brefeldin A