by Mark Wheeler

Scientists at City of Hope have discovered that chemicals in grape seed extract (GSE) — found in grape skin and seeds and even red wine — can suppress the production of estrogen, a major player in the development of breast cancer.

The research, by Shiuan Chen, Ph.D., director and professor, Department of Surgical Research, Ikuko Kijima, a fourth-year graduate student at City of Hope’s Graduate School of Biological Sciences, and colleagues, was reported in the June issue of Cancer Research. It follows earlier work by Chen that showed GSE inhibits estrogen’s activity.

Interestingly, the researchers found that GSE can suppress estrogen in cancerous tissue — which produces excess amounts of estrogen — without inhibiting critical estrogen production from healthy tissue. The findings could eventually lead to a preventive therapy that would help both pre- and post-menopausal women.

Approximately 70 percent of all breast cancers are driven by estrogen. For years, breast cancer researchers have targeted aromatase, an enzyme that converts androgen to the female hormone estrogen. Aromatase is normally expressed in a number of tissues, such as ovary, placenta, fat and bone. It is expressed at higher levels in breast cancer tissue than normal breast tissue.

In the Dec. 2003 issue of Cancer Research, Chen’s lab identified a class of chemical compounds called procyanidin dimers, which can be purified from red wine. They proved to be powerful inhibitors of aromatase activity and also reduced tumor growth in a mouse model.

Now the researchers have gone a step further and have shown that GSE can stop breast cancer cells from making the aromatase protein.

“We have demonstrated that grape seed extract can have a dual effect,” said Chen. “It can suppress aromatase activity, as well as its expression.”

Importantly, the researchers’ work demonstrates this suppression may be targeted to cancerous tissue. This is key to developing future preventive treatment, particularly for pre-menopausal women.

While aromatase inhibitors are effective in suppressing estrogen formation, patients have also experienced side effects associated with estrogen deficiency, such as bone loss. That is because current aromatase inhibitors suppress estrogen in the whole body.

Chen and his fellow researchers aim to design treatment strategies that selectively suppress aromatase expression in breast tumor tissue while maintaining estrogen levels in normal tissues. The discovery by Kijima, Chen and colleagues that GSE does indeed suppress aromatase expression in breast tumors suggests there are chemicals (not necessarily procyanidin dimers) in GSE that do this, and thus might ultimately be developed as cancer therapeutics.

“We believe these are exciting results because they demonstrate that GSE may be potentially useful in both the treatment as well as the prevention of hormone-dependent breast cancer,” said Chen.

Chen said his lab’s ongoing work is to identify the chemicals in GSE that are involved in suppressing estrogen, develop therapeutic drugs based on these chemicals, and eventually go to clinical trials for pre-menopausal women.