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WCRF/AICR
Global Network

AICR ScienceNow
Volume 20
Spring 2007

Inhibiting Aromatase via Foods

Blocking the production of estrogen is a relatively new drug pathway in cancer treatment. With AICR funding, a research team is finding that everyday foods may lower estrogen production in the same way.

It was only about ten years ago that aromatase inhibitors became available to treat and prevent recurrence of breast cancer. This novel class of drugs blocks the production of aromatase, an enzyme that converts androgen to estrogen. The resulting lower amount of estrogen slows or inhibits the growth of estrogen-sensitive breast tumors. Investigating how easily accessible foods also work as aromatase inhibitors has been a major focus of the laboratory of Shiuan Chen, Ph.D., Director of the Department of Surgical Research at the City of Hope in Duarte, California.

Initially, Dr. Chen and his colleagues found that a group of phytochemicals called procyanidin B dimer - part of the polyphenol family - were potent inhibitors of aromatase. Knowing that grape seeds are a rich source of procyanidin B, the researchers tested the aromatase-inhibiting ability of 13 brands of grape seed extracts. A series of both cell and animal studies found that 10 of the brands showed at least 80 percent inhibition of aromatase. "These findings encouraged us to screen a variety of vegetables to identify dietary sources for aromatase inhibitors," Dr. Chen says.

With funding from AICR, Dr. Chen tested seven vegetable extracts and found white button mushroom extract was most effective at preventing the production of aromatase. That led to investigating other mushroom varieties. Cell studies showed that shiitake, portabello, crimini and baby button mushrooms also had the ability to inhibit aromatase activity. Dr. Chen's group decided to proceed with white button mushrooms, because they are easily available in all seasons and cost less than other mushroom varieties.

Dr. Chen determined the active chemicals in each of the tested foods that inhibit estrogen production and identified the effective dosage.
For instance, in white button mushrooms he and his colleagues have pinpointed conjugated linoleic acid as having the key anti-aromatase effect in breast cancer cells. "Elucidating the mechanisms used in suppressing aromatase activity can contribute to designing prevention strategies that inhibit the aromatase in cancer cells, while maintaining estrogen levels in normal tissues," Dr. Chen notes.

Testing in Humans Beginning
Dr. Chen's research has laid the groundwork for human studies, and he has teamed up with oncologists at City of Hope to conduct clinical trials. "We've seen what happens in the test tube and in animals, and now we want to know whether this happens in people, and the effects of different dosages," he notes.

Already under way is a Phase I prevention trial to test the effect of four different concentrations of grape seed extract on estrogen suppression in women with risk factors for breast cancer. The trial is enrolling 24 women, ages 40 to 65, who will be divided into four groups. For 12 weeks, women in each group will consume a different amount of grape seed extract, ranging from a daily dose of 50 mg to 300 mg. Researchers will collect blood samples weekly. The goal of the trial is to determine the level of estrogen suppression in each group.

Next Target: Prostate Cancer
In addition to the aromatase-inhibiting properties of the mushrooms, Dr. Chen found that the fungi contain phytochemicals that suppress the enzyme 5-alpha-reductase. Prior research has found 5-alpha-reductase plays a role in the development of prostate cancer. With another grant from AICR, Dr. Chen is testing how different dosages of white button mushroom extract affect the development of prostate tumors in mice.

Early results have shown the mushrooms are effective in suppressing growth of prostate cancer, and Dr. Chen is working with clinical oncologists to plan Phase I trials in humans. "An effective cancer preventive agent should not significantly alter quality of life, and needs to be safe," Dr. Chen says, adding that both grape seeds and mushrooms are also inexpensive and therefore more readily available to underserved populations.

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