Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling

Publikace nespadá pod Lékařskou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.

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NEHYBOVÁ Tereza ŠMARDA Jan DANIEL Lukáš BREZOVSKÝ Jan BENEŠ Petr

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Steroid Biochemistry and Molecular Biology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://www.sciencedirect.com/science/article/pii/S0960076015001247
Doi http://dx.doi.org/10.1016/j.jsbmb.2015.04.019
Obor Genetika a molekulární biologie
Klíčová slova Breast cancer; Estrogen receptor; Phytoestrogen; Wedelolactone
Popis 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 II alpha. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at mu M concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) alpha and beta as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ER alpha or ER beta and by molecular docking of this coumestan into ligand binding pocket of both ER alpha and ER beta. 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.
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