The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1, both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα.
- MeSH
- alfa receptor estrogenů * metabolismus genetika MeSH
- endokrinní disruptory * farmakologie toxicita MeSH
- faktor TFF1 metabolismus genetika MeSH
- fenoly * farmakologie chemie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nádory prsu metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Trefoil peptidy patří do skupiny malých peptidů, jejichž exprese je místně i tkáňově specifická. Tyto peptidy by mohly být využity jako markery nádorového onemocnění dělohy. Typ studie: Experimentální studie. Název a sídlo pracoviště: Porodnicko-gynekologická klinika FN a LF UP, Olomouc; Oddělení klinické biochemie, Středomoravská nemocniční a.s., Nemocnice Prostějov. Metodika: V období od 2012 do 2015 podstoupilo osmdesát devět žen hysteroskopii a biopsii endometria pro krvácení v postmenopauze. U padesáti tří pacientek ve věku (průměr ± standardní odchylka) 63,4 ± 9,5 (33–80) let byl diagnostikován karcinom endometria, u šesti pacientek ve věku 62,9 ± 6,4 (55–74) let byla diagnostikována hyperplazie endometria a třicet pacientek ve věku 63,3 ± 9,3 (48–62) let s histologicky verifikovanou atrofií endometria tvořilo kontrolní soubor. V den výkonu byl každé pacientce odebrán vzorek venózní krve, který byl následně vyšetřen a byly stanoveny hladiny TFF1, TFF2 a TFF3. Výsledky: Hladiny TFF3 byly významně vyšší u pacientek s karcinomem endometria, ale ne ve skupině žen s endometriální hyperplazií. Hladiny TFF1 a TFF2 se v jednotlivých histopatologických skupinách významně nelišily. Závěr: Prokázali jsme zvýšené hladiny TFF3, ale ne TFF1 a TFF2 u pacientek s karcinomem endometria. U žen s endometriální hyperplazií nebyly hladiny TFF1, TFF2 a TFF3 zvýšeny.
Aim: Trefoil peptides are a family of small proteins that are expressed in a site-specific fashion by certain epithelial tissues. These peptides might be used as markers for neoplastic uterine disease. Design: Experimental study. Setting: Department of Obstetrics and Gynaecology, University Hospital, Medical Faculty, Palacký University, Olomouc; Department of Laboratory Biochemistry, Central Moravian Hospital Trust, Member of Agel holding, Prostějov. Methods: During the time period from 2012 to 2015 eighty-nine women underwent hysteroscopy and endometrial biopsy for postmenopausal bleeding. Fifty three patients, at the age of (mean ? standard deviation) 63,4 ± 9,5 (33–80) years were diagnosed with endometrial cancer, six patients at the age of 62,9 ± 6,4 (55–74) years were diagnosed with endometrial hyperplasia and thirty patients at the age of 63,3 ± 9,3 (48–62) years diagnosed with endometrial atrophy represented control group. At the day of surgery the venous blood was sampled and subsequently examined for the levels of TFF1, TFF2 and TFF3. Results: TFF3 levels were significantly higher in patients with endometrial carcinoma but not in endometrial hyperplasia subgroup. The levels of TFF1 and TFF2 were not different in selected histopathological subgroups. Conclusion: We have shown elevated levels of TFF3 but not of TFF1 and TFF2 in patients with endometrial cancer. TFF1, TFF2 and TFF3 levels were not elevated in patients with endometrial hyperplasia.
- MeSH
- faktor TFF1 analýza krev MeSH
- faktor TFF2 analýza krev MeSH
- faktor TFF3 * analýza krev MeSH
- hysteroskopie MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádory endometria * diagnóza chirurgie MeSH
- senioři MeSH
- sérologické testy metody MeSH
- trefoil proteiny * analýza krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH