Translation of grape seed extract as a natural aromatase inhibitor for breast cancer prevention.

B166

Suppression of estrogen biosynthesis through aromatase inhibition is thought to have potential for chemoprevention of breast cancer. While pharmaceutical agents have an established therapeutic role, examination of foods and dietary compounds for cancer prevention is being explored. A research project was initiated in our laboratory to investigate whether any fruits contain phytochemicals that can inhibit aromatase. We found that of seven fruit juices tested, grape juice was the most effective in inhibiting the activity of human placental aromatase activity. Over the last several years, we have learned that a methanol extract of grape juice inhibits aromatase in a dose-dependent manner; the extract suppresses the proliferation of an aromatase over-expressing and estrogen receptor-positive breast cancer cell line, MCF-7aro; and oral administration of the extract completely abrogates aromatase-induced hyperplasia and other changes in the mammary tissue of aromatase transgenic mice. Procyanidin B dimers, the major phytochemicals in the seeds and skins of grapes, were found to be the chemicals responsible for the anti-aromatase activity. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress peripheral estrogen formation. Grape seed extract (GSE) is a common dietary supplement that has been found to contain high levels of procyanidin B dimers. We examined the ability of various manufactured brands of to inhibit human placental aromatase. We found that not all brands of GSE have equivalent anti-aromatase activity. GSE, which is rich in procyanidin B dimers, inhibits the growth of mammary tumors in nude mice when orally administered. A GSE demonstrated to significantly inhibit aromatase was associated with reduced androgen-dependent MCF-7aro tumor growth in nude mice when orally administered. Based on this preclinical data, we hypothesize that women could reduce their breast cancer risk with a GSE dietary supplement through suppression of estrogen biosynthesis. A Phase I chemoprevention trial to evaluate the anti-aromatase activity of GSE in post-menopausal women is underway to test this hypothesis. The design of this clinical trial will be presented.