Abstract

Aromatase (CYP19) converts androgens to estrogens. By synthesizing estrogens, aromatase (especially tumor aromatase) is thought to play an important role in promoting breast cancer growth in postmenopausal women. By inhibiting estrogen biosynthesis, aromatase inhibitors, including phytochemicals, are potential chemopreventive agents for breast cancer. Our recent aromatase inhibition experiments have revealed that grape juice contains compounds that inhibit aromatase. Inhibition kinetic analysis indicates that the active components in grape juice inhibit aromatase by competing for the binding of the substrate androstenedione. Results from cell culture experiments suggest that chemicals in grape juice can act as weak agonists/antagonists of estrogen receptor and as aromatase inhibitors. Finally, the breast cancer-protective action of grape juice was demonstrated with a nude mouse model using MCF7aro, an aromatase-transfected MCF-7 cell line. It was found that the tumor size in mice fed (by gavage) with 0.5 ml of grape juice/day for 5 weeks is reduced 70% by comparing to the tumor size in the animals not fed with grape juice. Our finding suggests that grape juice may be useful in breast cancer prevention by inhibiting in situ aromatase/estrogen biosynthesis.

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