No evidence for the in vivo activity of aromatase-inhibiting flavonoids.
Measurements of the aromatase-inhibiting and antioxidative capacities of flavonoids in vitro showed that slight changes in flavonoid structure may result in marked changes in biological activity. Several flavonoids such as 7-hydroxyflavone and chrysin (5,7-dihydroxyflavone) were shown to inhibit the formation of 3H-17beta-estradiol from 3H-androstenedione (IC(50)<1.0 microM) in human choriocarcinoma JEG-3 cells and in human embryonic kidney cells HEK 293 transfected with human aromatase gene (Arom+HEK 293). Flavone and quercetin (3,3',4',5,7-pentahydroxyflavone) showed no inhibition (IC(50)>100 microM). None of the requirements for optimal antioxidative capacity (2,3-double bond with 4'-hydroxy group, 3-hydroxyl group, 5,7-dihydroxy structure and the orthodihydroxy structure in the B-ring) is relevant for the maximum inhibition of aromatase by flavonoids. After oral administration to immature rats at a dose of 50 mg/kg body weight, which considerably exceeds amounts found in daily human diets, neither aromatase-inhibiting nonestrogenic flavonoids, such as chrysin, nor estrogenic flavonoids, such as naringenin and apigenin, induced uterine growth or reduced estrogen- or androgen-induced uterine growth. The inability of flavonoids to inhibit aromatase and, consequently, uterine growth in short-term tests may be due to their relatively poor absorption and/or bioavailability.
Saarinen
N
N
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland. nisaarin@utu.fi
Joshi
S C
SC
Ahotupa
M
M
Li
X
X
Ammälä
J
J
Mäkelä
S
S
Santti
R
R
D000735:Androstenedione / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000517:prevention & control; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051381:Rats; D013329:Structure-Activity Relationship; D014162:Transfection; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
D000975:Antioxidants; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase