Aromatase and 17 β-hydroxysteroid dehydrogenase inhibition by flavonoids

• Published in: Cancer letters Vol. 133; no. 1; pp. 101 - 106
• Main Authors: Le Bail, J.C, Laroche, T, Marre-Fournier, F, Habrioux, G
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 13-11-1998; Elsevier
• Subjects: 17 β-Hydroxysteroid dehydrogenase; Analysis; Aromatase; Biological and medical sciences; Flavonoids; General pharmacology; Medical sciences; Pharmacology. Drug treatments; 17 β-Hydroxysteroid dehydrogenase; Flavonoids; Aromatase; Human; Enzyme; Estimation; 17β-Estradiol; HPLC chromatography; Enzyme inhibitor; Estrogen synthase; Microsome; Radioactivity detector; Flavonoid; Placenta; Structure activity relation; Estrone; Quantitative analysis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(98)00211-0

A method for estimating in the same assay both aromatase and 17
β-hydroxysteroid dehydrogenase activities in human placental microsomes using radiolabelled [1,2,6,7-
3H]4-androstene-3,17-dione was proposed. In this assay, estrone (E
1) and estradiol (E
2) produced were separated by HPLC and estimated using a radioactive flow detector. Using this method, the inhibitory effect of various flavonoids, including flavone, flavanone and isoflavone, on the human placental aromatase and 17
β-hydroxysteroid dehydrogenase was studied. Flavonoids were shown to be potent inhibitors of both aromatase and 17
β-hydroxysteroid dehydrogenase activities. We found that 7-hydroxyflavone and apigenin are the most effective aromatase and 17
β-hydroxysteroid dehydrogenase inhibitors, respectively. Experiments showed that a hydroxyl group in position 7 was essential for anti-17
β-hydroxysteroid dehydrogenase activity. However, flavonoids with 7-methoxy or 8-hydroxyl groups on the A ring showed only anti-aromatase activity. Structure–activity relationships were discussed.