Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro.
| dc.contributor.author | Berényi, Agnes | |
| dc.contributor.author | Frotscher, Martin | |
| dc.contributor.author | Marchais-Oberwinkler, Sandrine | |
| dc.contributor.author | Hartmann, Rolf W | |
| dc.contributor.author | Minorics, Renáta | |
| dc.contributor.author | Ocsovszki, Imre | |
| dc.contributor.author | Falkay, George | |
| dc.contributor.author | Zupkó, István | |
| dc.date.accessioned | 2013-08-15T09:51:45Z | |
| dc.date.available | 2013-08-15T09:51:45Z | |
| dc.date.issued | 2013-08 | |
| dc.identifier.citation | Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro. 2013, 28 (4):695-703 J Enzyme Inhib Med Chem | en_GB |
| dc.identifier.issn | 1475-6374 | |
| dc.identifier.pmid | 22471733 | |
| dc.identifier.doi | 10.3109/14756366.2012.672414 | |
| dc.identifier.uri | http://hdl.handle.net/10033/298375 | |
| dc.description.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. | |
| dc.language.iso | en | en |
| dc.rights | Archived with thanks to Journal of enzyme inhibition and medicinal chemistry | en_GB |
| dc.title | Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro. | en |
| dc.type | Article | en |
| dc.contributor.department | Department of Pharmacodynamics and Biopharmacy, University of Szeged , Szeged , Hungary. | en_GB |
| dc.identifier.journal | Journal of enzyme inhibition and medicinal chemistry | en_GB |
| refterms.dateFOA | 2014-08-15T00:00:00Z | |
| html.description.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. |
