Aromatase inhibition by bioavailable methylated flavones

Abstract

Previous studies have shown chrysin, 7-hydroxyflavone and 7,4'-dihydroxyflavone to be the most potent flavonoid inhibitors of aromatase. However, very poor oral bioavailability is a major limitation for the successful use of dietary flavonoids as chemopreventive agents. We have recently shown that methylated flavones, including 5,7-dimethoxyflavone, 7-methoxyflavone and 7,4'-dimethoxyflavone, are much more resistant to metabolism than their unmethylated analogs and have much higher intestinal absorption. In this study, we examined these fully methylated flavones as potential aromatase inhibitors for the prevention and/or treatment of hormone-dependent cancers. Whereas 5,7-dimethoxyflavone had poor effect compared to its unmethylated analog chrysin, 7-methoxyflavone and 7,4'-dimethoxyflavone were almost equipotent to their unmethylated analogs with IC(50) values of 2-9 microM. Thus, some fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents.

Fig. 1

Structures of flavones used in this study.

Fig. 2

Effect of 5,7-DMF compared to chrysin (A), 7-MF compared to 7-HF (B), and 7,4′-DMF compared to 7,4′-DHF (C) on aromatase activity. □, methylated flavones; ●, unmethylated flavones. The data are expressed as percent of control. Mean values ± SEM (in many cases smaller than the symbols) are shown (n = 4 - 10).