Phytoestrogens like the naturally occurring naringenin and its derivatives are appointed
for their estrogenic activity. Some flavonoids of Naringenin matrix e.g. 8-prenylnaringenin
(8-PN) and 6-(1,1-dimethylallyl)naringenin (6-DMAN) have already been shown as belonging
to the most potent phytoestrogenic substances. Phytoestrogens have been discussed
to act as chemo protective substances for example against breast cancer menopausal
disorders. Almost nothing is known about other than estrogen receptor mediated actions.
Because there are some evidences for anti-androgenic properties of estrogen-like compounds
we tested 8-PN, 6-DMAN and naringenin in two independent (anti-)androgen screening
assays. First using a yeast-based androgen receptor assay relatively strong anti-androgen
activities were demonstrated for 6-DMAN and 8-PN, while the parent compound naringenin
did not show recognizable anti-androgen activity. In an androgen receptor activity
assay based on the analysis of prostate specific antigen (PSA) concentrations in the
supernatants of treated PC3(AR)2 cells the anti-androgenic activity of 6-DMAN was
detected at concentrations of 10–5 M. 8-Prenylnaringenin or naringenin showed no anti-androgenic
effect. In summary, for the first time we provide evidence of the anti-androgenic
activity of 6-DMAN in two independent model systems. In conclusion, we demonstrated
a bi-modular activity of the naturally occurring naringenin derivatives 6-(1,1-dimethylallyl)naringenin
and 8-prenylnaringenin. These prenylated naringenins not only to act via the estrogen
receptor but also through the androgen receptor.
