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

作者：Berenyi Agnes; Frotscher Martin; Marchais Oberwinkler Sandrine; Hartmann Rolf W; Minorics Renata; Ocsovszki Imre; Falkay George; Zupko Istvan^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, 28(4): 695-703.

DOI：10.3109/14756366.2012.672414

• Cancer cell
• apoptosis
• cell cycle

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 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-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 17 beta-HSD1-inhibiting capacity. These results indicate that it is possible to combine direct antiproliferative activity and 17 beta-HSD1 inhibition resulting in novel agents with dual mode of action.

• 出版日期2013-8