Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.
This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.
Hundertmark
S
S
Department of Obstetrics and Gynaecology, Klinikum Benjamin Franklin, Freien Universität Berlin, Germany.
Bühler
H
H
Rudolf
M
M
Weitzel
H K
HK
Ragosch
V
V
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000287:Administration, Topical; D000616:Aminoglutethimide / Q000494:pharmacology; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D047072:Aromatase Inhibitors; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000627:therapeutic use*; D006034:Glycyrrhetinic Acid / Q000627:therapeutic use*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011239:Prednisolone / Q000378:metabolism / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D005938:Glucocorticoids; D013629:Tamoxifen; D000616:Aminoglutethimide; D003907:Dexamethasone; D011239:Prednisolone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid