Suppression of aromatase (estrogen synthetase) by red wine phytochemicals

Estrogen promotes the proliferation of breast cancer cells. Aromatase is the enzyme that converts androgen to estrogen. In tumors, the expression of aromatase is upregulated compared to surrounding non-cancerous tissue. In this study, we found that wine contains phytochemicals that are capable of suppressing aromatase. Red wine was shown to be much more effective than white wine in the suppression of aromatase activity. Whole wine, lyophilized wine, and heat-treated extracts were examined for aromatase inhibition in a human placenta microsomal assay. C18 Sep-Pak cartridge (Waters Co.) separation of red wine extracts under an increasing acetonitrile (ACN) gradient found that the most active components were in the 20% ACN fraction, in that they inhibited the wild-type human placenta aromatase, wild-type porcine placenta and blastocyst aromatase in a dose-dependent fashion. The 20% ACN active fraction was heat stable and inhibited aromatase in a non-competitive manner. The aromatase-inhibitory action of red wine extracts was also examined with a transgenic mouse model in which aromatase is over-expressed in the mammary tissues. It was found that the intake of the 20% ACN fraction by gavage completely abrogated aromatase-induced hyperplasia and other changes in the mammary tissue. This is the first report demonstrating that wine, especially red wine, contains phytochemicals that can inhibit aromatase.