Researchers have developed a new synthetic compound, derived from a known anti-cancer agent found in broccoli, that they say could become a pill to prevent breast cancer, and, possibly, other forms as well.

Finding compounds to prevent cancer is a Holy Grail of medical research. Right now, Tamoxifen is the only drug approved by the FDA to prevent breast cancer, but it is effective only in women whose cancers are estrogen-dependent. The new compound, called oxomate, could have a much wider application.

In a test study, female rats who had been given carcinogens and who were fed oxomate had up to a 50 percent reduction in the number of breast tumors compared with similarly treated rats given a regular diet.

"It definitely has a lot of potential," says Jerome Kosmeder, lead author of the study, which was presented last night at the annual meeting of the American Chemical Society in Boston. "The public knows that prevention is better than trying to treat something. Right now the government is trying to do what it can, but I think private industry needs to step in and take charge."

Other experts are not so sure about this new finding. "You never know when something might be really great. The problem is it has never been tried in a human," says Dr. Alan J. Stolier, medical director of the Lieselotte Tansey Breast Center at the Ochsner Clinic Foundation in New Orleans. "There has not been one human test on it. I'm amazed at how much press something can get that was given to rats."

Kosmeder, who is also a research assistant professor at the College of Pharmacy at the University of Illinois at Chicago, estimates that a pill could be ready for human trials in seven to 10 years.

Researchers at Johns Hopkins University in Baltimore had already identified sulforaphane as a natural cancer-preventing agent found in broccoli and other cruciferous vegetables such as cabbage and Brussels sprouts. Sulforaphane, however, is toxic in high doses and is difficult and expensive to produce.

The new compound, oxomate, acts the same way as its natural counterpart sulforaphane, but has been engineered to be less toxic. In tests on cultured liver cells, oxomate was seven times less toxic than sulforaphane. Oxomate can also be produced synthetically in large quantities.

Like sulforaphane, oxomate increases the number of Phase II (detoxification) enzymes needed to protect cells from damage by carcinogens.

"Phase II enzymes are sort of our body's protection against internal and external compounds that can damage DNA," Kosmeder says. "This compound and that in broccoli work by elevating these enzyme levels beyond what would abnormally be there. They're boosting your own body's defense against carcinogens."

Basically, oxomate prevents normal cells from becoming cancer cells by blocking the action of carcinogens. Though the researchers so far only have results in breast cancer, they think oxomate may have a role to play with colon, skin and lung cancer.

The idea would be to give oxomate in pill form to people who have been exposed to carcinogens or who, for whatever reason, have a predisposition to the disease. "You take a vitamin every day, and this is the same idea," Kosmeder says. "You want to keep up your natural enzyme levels to keep protecting your body."

Even though prevention is a huge area of medical research, it is also a time-consuming expensive one. Trials for drugs to treat diseases may take one to two years, whereas trials to test preventives can take five to 10 years to complete.

Kosmeder and his colleagues are trying to find ways to shorten that time by locating biochemical markers to measure the action of oxomate.

"It is very, very difficult to prove that something prevents something from happening," Stolier says.

And he knows from experience. "Many years ago when I had a lab, I learned that you could take a mouse or rat, inject the solution of destroyed cancer cells into the mouse and then in a few weeks that mouse wouldn't get that kind of cancer. You can immunize the mouse against cancer, but we haven't done that to humans. We've tried. It just doesn't seem to work."

What To Do

For more information on breast cancer prevention and treatment, visit the National Cancer Institute or the Food and Drug Administration.

SOURCES: Alan J. Stolier, M.D., medical director, Lieselotte Tansey Breast Center, Ochsner Clinic Foundation, New Orleans; Jerome Kosmeder, Ph.D, research assistant professor, College of Pharmacy, University of Illinois at Chicago; Aug. 18, 2002, presentation, American Chemical Society annual meeting, Boston

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