Aromatase and 17 β-hydroxysteroid dehydrogenase inhibition by flavonoids

• Published in: Cancer letters 1998-11, Vol.133 (1), p.101-106
• Main Authors: Le Bail, J.C, Laroche, T, Marre-Fournier, F, Habrioux, G
• Format: Article
• Language: English
• Subjects: 17 β-Hydroxysteroid dehydrogenase; Analysis; Aromatase; Biological and medical sciences; Flavonoids; General pharmacology; Medical sciences; Pharmacology. Drug treatments
• 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.