Wedelolactone Induces Growth of Breast Cancer Cells by Stimulation of Estrogen Receptor Signalling

Authors

Nehybova, T., Smarda, J., Daniel, L., Brezovsky, J., Benes, P.

Source

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 152: 76-83 (2015)

Abstract

Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.

Full text

Citation

Nehybova, T., Smarda, J., Daniel, L., Brezovsky, J., Benes, P., 2015: Wedelolactone Induces Growth of Breast Cancer Cells by Stimulation of Estrogen Receptor Signalling. Journal of Steroid Biochemistry and Molecular Biology 152: 76-83.

Daniel’s Success in Students` Professional Activities
Three New Masters of Science: Zuzana, Martin and Pavel
Joseph Fourier Prize for Milos
The Dean’s Award for Veronika
A New Addition to the Team: Verunka
The Best Poster Award for Milos Musil
Martin the Winner of Sigma-Aldrich Competition