Tectoridin, a poor ligand of estrogen receptor alpha, exerts its estrogenic effects via an ERK-dependent pathway

Mol Cells. 2009 Mar 31;27(3):351-7. doi: 10.1007/s10059-009-0045-8. Epub 2009 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Breast Neoplasms / metabolism
  • Butadienes / pharmacology
  • Cell Line, Tumor
  • Cyclic AMP / metabolism
  • Drug Interactions
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Genistein / pharmacology
  • Humans
  • Isoflavones / antagonists & inhibitors
  • Isoflavones / pharmacology*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nitriles / pharmacology
  • Phosphorylation
  • Phytoestrogens / pharmacology
  • Signal Transduction / drug effects


  • Butadienes
  • Estrogen Receptor alpha
  • Isoflavones
  • Nitriles
  • Phytoestrogens
  • U 0126
  • Estradiol
  • tectoridin
  • Genistein
  • Cyclic AMP
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3