Soy
isoflavones have been studied extensively for estrogenic and antiestrogenic properties. Other
flavonoids, found in fruits, vegetables,
tea and wine, have been much less tested for
steroid hormone activity. We therefore assessed the estrogenic, androgenic and progestational activities of 72
flavonoids and structurally-related compounds. These compounds were tested on BT-474 human
breast cancer cells at concentrations of 10(8)-10(-5) M, with
estradiol (
estrogen),
norgestrel (
progestin) and
dihydrotestosterone (
androgen) used as positive controls, and
ethanol (
solvent) as a negative control. pS2, an
estrogen-regulated protein, and
prostate-specific antigen (PSA), regulated by
androgens and
progestins, were quantified in tissue culture supernatants using ELISA-type immunofluorometric assays developed in-house. Of the 72 compounds tested, 18 showed estrogenic activity
at 10(-5) M. Of this subset, seven also showed progestational activity at this concentration. The soy
isoflavones,
biochanin A and
genistein, showed the most potent estrogenic activity, with a dose-response effect up to 10(-7) M. Of all other
flavonoids,
luteolin and
naringenin displayed the strongest estrogenicity, while
apigenin had a relatively strong progestational activity. Based on our data, we have formulated a set of structure/function relationships between the tested compounds.
Flavonoids, therefore, exhibit significant
steroid hormone activity, and may have an effect in the modification of
cancer risk by diet, or in
cancer therapeutics and prevention.