Grape Seed Found to Be a Natural Aromatase Inhibitor

BOSTON—Grape seed extract was effective in inhibiting the enzyme aromatase in both cell culture and animal studies, according to researchers from the City of Hope, Duarte, California. A phase I prevention trial is now underway to test whether this extract lowers estrogen levels in healthy postmenopausal women, and, if so, which dose is the most effective.

"We wanted to screen several food products for aromatase inhibitory activity, test their ability to suppress hormone-induced breast cancer proliferation, and then translate these findings into clinical trials," said Melanie Palomares, MD, a medical oncologist at the City of Hope Comprehensive Cancer Center Cancer Screening & Prevention Program.

Dr. Palomares presented the results at the Third International Conference of the Society for Integrative Oncology (poster C021).

The researchers, led by Shiuan Chen, PhD, professor and director of surgical research at City of Hope's Beckman Research Institute, found that of seven fruit juices tested, grape juice was the most effective at inhibiting aromatase activity in cell culture assay. In further studies, they found that a methanol extract of grape juice inhibited aromatase in a dose-dependent manner. This extract also suppressed the proliferation of an aromatase overexpressing and ER-positive breast cancer cell line, MCF-7Aro.

Tumor Growth Reduced

When the grape seed extract was fed to mice that had been injected with breast cancer cells, tumor growth was reduced in a dose-dependent manner. In addition, hyperplasia and other abnormal changes of the breast seen in aromatase transgenic mice were reversed by oral administration of the extract.

The compounds responsible for the inhibitory effects of aromatase activity are procyanidins. Procyanidin B dimers are phytochemicals found in the seeds and skins of grapes. The dimers were tested with the same xenograft models used with the grape seed extract, and were found to reduce tumor growth.

Since grape seed extract is a common dietary supplement, various manufactured brands were tested for their concentration of procyanidin B dimers, and their ability to inhibit human aromatase in a cell assay.

"Investigators in Dr. Chen's lab tested 13 different brands and found a lot of variability," Dr. Palomares said. "Two brands didn't inhibit at all, while 10 showed at least 80% inhibition of aromatase activity." One of the 10 was chosen for further development.

Phase I Trial

A phase I trial co-sponsored by the California Breast Cancer Research Program and the National Cancer Institute is currently recruiting patients. Each of four doses of grape seed extract will be tested in healthy women ages 40 to 75 with no history of breast cancer or DCIS and no recent use of endocrine therapy, including oral contraceptives, hormone-replacement therapy, SERMs, or aromatase inhibitors.

The primary endpoint will be the level of estrogen suppression as measured by pre- and post-treatment changes in serum estradiol, estrone, and estrone sulfate. The effect of grape seed extract on lipids and markers of bone resorption will also be evaluated.