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: Kyungsu Kang, Saet Byoul Lee, Sang Hoon Jung, Kwang Hyun Cha, Woo Dong Park, Young Chang Sohn, Chu Won Nho
• Journal: Molecules and cells (Mol Cells) Vol. 27 Issue 3 Pg. 351-7 (Mar 31 2009) ISSN: 0219-1032 [Electronic] Korea (South)
• PMID: 19326083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pharmacology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Nitriles (pharmacology)
• Phosphorylation
• Phytoestrogens (pharmacology)
• Signal Transduction (drug effects)