Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25934092
DOI
10.1016/j.jsbmb.2015.04.019
PII: S0960-0760(15)00124-7
Knihovny.cz E-resources
- Keywords
- Breast cancer, Estrogen receptor, Phytoestrogen, Wedelolactone,
- MeSH
- Transcriptional Activation genetics MeSH
- Estrogen Receptor alpha metabolism MeSH
- Estrogen Receptor Antagonists pharmacology MeSH
- Estrogen Receptor beta metabolism MeSH
- Estradiol analogs & derivatives pharmacology MeSH
- Estrogens pharmacology MeSH
- Fulvestrant MeSH
- HEK293 Cells MeSH
- Coumarins pharmacology MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents pharmacology MeSH
- Response Elements genetics MeSH
- Signal Transduction drug effects MeSH
- Molecular Docking Simulation MeSH
- Transcription Factor AP-1 metabolism MeSH
- Binding Sites drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Estrogen Receptor alpha MeSH
- Estrogen Receptor Antagonists MeSH
- Estrogen Receptor beta MeSH
- ESR1 protein, human MeSH Browser
- Estradiol MeSH
- estrogen receptor beta isoform M, human MeSH Browser
- Estrogens MeSH
- Fulvestrant MeSH
- Coumarins MeSH
- Antineoplastic Agents MeSH
- Transcription Factor AP-1 MeSH
- wedelolactone MeSH Browser
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.
References provided by Crossref.org
Transcription factor c-Myb: novel prognostic factor in osteosarcoma
Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells
