Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

Abstract	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.
Authors	S Hundertmark, H Bühler, M Rudolf, H K Weitzel, V Ragosch
Journal	The Journal of endocrinology (J Endocrinol) Vol. 155 Issue 1 Pg. 171-80 (Oct 1997) ISSN: 0022-0795 [Print] England
PMID	9390020 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents Antineoplastic Agents, Hormonal Aromatase Inhibitors Glucocorticoids Tamoxifen Aminoglutethimide Dexamethasone Prednisolone Hydroxysteroid Dehydrogenases 11-beta-Hydroxysteroid Dehydrogenases Glycyrrhetinic Acid
Topics	11-beta-Hydroxysteroid Dehydrogenases Administration, Topical Aminoglutethimide (pharmacology) Analysis of Variance Anti-Inflammatory Agents (therapeutic use) Antineoplastic Agents, Hormonal (pharmacology) Aromatase Inhibitors Breast (enzymology) Breast Neoplasms (drug therapy, enzymology) Carcinoma, Intraductal, Noninfiltrating (drug therapy, enzymology) Cell Division (drug effects) Cells, Cultured Dexamethasone (metabolism, therapeutic use) Female Glucocorticoids (metabolism, therapeutic use) Glycyrrhetinic Acid (therapeutic use) Humans Hydroxysteroid Dehydrogenases (antagonists & inhibitors, metabolism) Prednisolone (metabolism, therapeutic use) Tamoxifen (pharmacology) Tumor Cells, Cultured

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