Počet záznamů: 1
Small change – big consequence: The impact of C15-C16 double bond in a D‑ring of estrone on estrogen receptor activity
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SYSNO ASEP 0575940 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Small change – big consequence: The impact of C15-C16 double bond in a D‑ring of estrone on estrogen receptor activity Tvůrce(i) Voňka, Petr (UEB-Q) ORCID
Rárová, L. (CZ)
Bazgier, V. (CZ)
Tichý, V. (CZ)
Kolářová, T. (CZ)
Holčáková, J. (CZ)
Berka, K. (CZ)
Kvasnica, Miroslav (UEB-Q) RID, ORCID
Oklešťková, Jana (UEB-Q) RID, ORCID, SAI
Kudová, Eva (UOCHB-X) RID, ORCID
Strnad, Miroslav (UEB-Q) RID, ORCID
Hrstka, Roman (UEB-Q) ORCIDCelkový počet autorů 12 Číslo článku 106365 Zdroj.dok. Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier - ISSN 0960-0760
Roč. 233, OCT (2023)Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Apoptosis ; Docking of steroid library ; Estrogen receptor alpha ; Luciferase assay ; Mitochondrial membrane potential Obor OECD Biochemistry and molecular biology CEP LM2023055 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura e-INFRA CZ - 90140 - CESNET, zájmové sdružení právnických osob
BBMRI.cz IV - 90233 - Masarykův onkologický ústavZpůsob publikování Open access Institucionální podpora UEB-Q - RVO:61389030 ; UOCHB-X - RVO:61388963 UT WOS 001048999000001 EID SCOPUS 85165571434 DOI https://doi.org/10.1016/j.jsbmb.2023.106365 Anotace Estrogen receptor alpha (ER) is a key biomarker for breast cancer, and the presence or absence of ER in breast and other hormone-dependent cancers decides treatment regimens and patient prognosis. ER is activated after ligand binding typically by steroid. 2682 steroid compounds were used in a molecular docking study to identify novel ligands for ER and to predict compounds that may show anticancer activity. The effect of the most promising compounds was determined by a novel luciferase reporter assay. Two compounds, 7 and 12, showing ER inhibitory activity comparable to clinical inhibitors such as tamoxifen or fulvestrant were selected. We propose that the inhibitory effect of compounds 7 and 12 on ER is related to the presence of a double bond in their D-ring, which may protect against ER activation by reducing the electron density of the keto group, or may undergo metabolism leading to an active compound. Western blotting revealed that compound 12 decreased the level of ER in the breast cancer cell line MCF7, which was associated with reduced expression of both isoforms of the progesterone receptor, a well-known downstream target of ER. However, compound 12 has a different mechanism of action from fulvestrant. Furthermore, we found that compound 12 interferes with mitochondrial functions, probably by disrupting the electron transport chain, leading to induction of the intrinsic apoptotic pathway even in ER-negative breast cancer cells. In conclusion, the combination of computational and experimental methods shown here represents a rapid approach to determine the activity of compounds towards ER. Our data will not only contribute to research focused on the regulation of ER activity but may also be useful for the further development of novel steroid receptor-targeted drugs applicable in clinical practice. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2024 Elektronická adresa https://doi.org/10.1016/j.jsbmb.2023.106365
Počet záznamů: 1