Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro.

2.50
Hdl Handle:
http://hdl.handle.net/10033/298375
Title:
Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro.
Authors:
Berényi, Agnes; Frotscher, Martin; Marchais-Oberwinkler, Sandrine; Hartmann, Rolf W; Minorics, Renáta; Ocsovszki, Imre; Falkay, George; Zupkó, István
Abstract:
Inhibition of the local formation of estrogens seems to be an attractive strategy for pharmacological intervention in hormone-dependent disorders. The direct antiproliferative properties of ten nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors were investigated on human cancer cell lines of gynecological origin. The mechanism of the antiproliferative action was approximated by cell cycle analysis, fluorescent microscopy, BrdU assay, determination of caspase-3 activity and quantification of the expression of cell cycle regulators at mRNA level. Treatment of HeLa cells with some of the compounds resulted in a concentration-dependent inhibition of the G1-S transition and an increase in the apoptotic population. The most effective agents increased the expression of tumor suppressors p21 and p53, while CDK2 and Rb were down-regulated. The reported anticancer actions of the tested compounds are independent of the 17β-HSD1-inhibiting capacity. These results indicate that it is possible to combine direct antiproliferative activity and 17β-HSD1 inhibition resulting in novel agents with dual mode of action.
Affiliation:
Department of Pharmacodynamics and Biopharmacy, University of Szeged , Szeged , Hungary.
Citation:
Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro. 2013, 28 (4):695-703 J Enzyme Inhib Med Chem
Journal:
Journal of enzyme inhibition and medicinal chemistry
Issue Date:
Aug-2013
URI:
http://hdl.handle.net/10033/298375
DOI:
10.3109/14756366.2012.672414
PubMed ID:
22471733
Type:
Article
Language:
en
ISSN:
1475-6374
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorBerényi, Agnesen_GB
dc.contributor.authorFrotscher, Martinen_GB
dc.contributor.authorMarchais-Oberwinkler, Sandrineen_GB
dc.contributor.authorHartmann, Rolf Wen_GB
dc.contributor.authorMinorics, Renátaen_GB
dc.contributor.authorOcsovszki, Imreen_GB
dc.contributor.authorFalkay, Georgeen_GB
dc.contributor.authorZupkó, Istvánen_GB
dc.date.accessioned2013-08-15T09:51:45Z-
dc.date.available2013-08-15T09:51:45Z-
dc.date.issued2013-08-
dc.identifier.citationDirect antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro. 2013, 28 (4):695-703 J Enzyme Inhib Med Chemen_GB
dc.identifier.issn1475-6374-
dc.identifier.pmid22471733-
dc.identifier.doi10.3109/14756366.2012.672414-
dc.identifier.urihttp://hdl.handle.net/10033/298375-
dc.description.abstractInhibition of the local formation of estrogens seems to be an attractive strategy for pharmacological intervention in hormone-dependent disorders. The direct antiproliferative properties of ten nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors were investigated on human cancer cell lines of gynecological origin. The mechanism of the antiproliferative action was approximated by cell cycle analysis, fluorescent microscopy, BrdU assay, determination of caspase-3 activity and quantification of the expression of cell cycle regulators at mRNA level. Treatment of HeLa cells with some of the compounds resulted in a concentration-dependent inhibition of the G1-S transition and an increase in the apoptotic population. The most effective agents increased the expression of tumor suppressors p21 and p53, while CDK2 and Rb were down-regulated. The reported anticancer actions of the tested compounds are independent of the 17β-HSD1-inhibiting capacity. These results indicate that it is possible to combine direct antiproliferative activity and 17β-HSD1 inhibition resulting in novel agents with dual mode of action.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of enzyme inhibition and medicinal chemistryen_GB
dc.titleDirect antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacodynamics and Biopharmacy, University of Szeged , Szeged , Hungary.en_GB
dc.identifier.journalJournal of enzyme inhibition and medicinal chemistryen_GB

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