title: Tectoridin, a poor ligand of estrogen receptor alpha, exerts its estrogenic effects via an ERK-dependent pathway.
abstract: Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, 17beta-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER alpha as compared to 17beta-estradiol and genistein. Despite poor binding to ER alpha, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER alpha at Ser(118). It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology Gangneung Institute, Gangneung 210-340, Korea.
authors.forename: Kyungsu
authors.initials: K
authors.lastname: Kang
authors.forename: Saet Byoul
authors.initials: SB
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jung
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Cha
authors.forename: Woo Dong
authors.initials: WD
authors.lastname: Park
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Sohn
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho