Direct antiproliferative effect of nonsteroidal 17beta-hydroxysteroid dehydrogenase type 1 inhibitors in vitro
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 canc...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2013
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| Sorozat: | JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
28 No. 4 |
| Tárgyszavak: | |
| doi: | 10.3109/14756366.2012.672414 |
| mtmt: | 1900266 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/39785 |
| Tartalmi kivonat: | 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. |
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| Terjedelem/Fizikai jellemzők: | 695-703 |
| ISSN: | 1475-6366 |