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WCRF/AICR
Global Network
AICR ScienceNow
Volume 15
Winter 2006

Synergy Among Cruciferous Phytochemicals

At the most recent AICR International Research Conference, Matthew Wallig, D.V.M., Ph.D., shared the results of his latest research. He has discovered that the understudied phytochemical crambene in cruciferous vegetables is more active when combined with another phytochemical, indole 3-carbinol (I3C). With further studies, these compounds could become part of a treatment for liver cancer.

Originally, Dr. Wallig, Professor of Comparative Pathology at the University of Illinois at Urbana-Champaign, did not intend to study the phytochemical crambene. He wanted to look at sulforaphane, a well-known phytochemical found in cruciferous vegetables, but it was very expensive and hard to purify. Since his laboratory had access to crambene, which had been isolated for use in some earlier experiments, he decided to test it.

"It's an overlooked phytochemical," Dr. Wallig says. Although experiments with cells in culture studies showed that this phytochemical was not very potent, work by his laboratory and others has shown that crambene is in fact highly active in live animals. The best source for this phytochemical is Brussels sprouts, although it's also found in certain varieties of broccoli.

At the 2005 AICR summer international research conference, Dr. Wallig presented his latest findings on the synergistic effects between crambene and the well-known phytochemical I3C.

2 + 2 = 6

Both I3C and crambene are known to activate phase 2 enzymes, which are important detoxification enzymes that help the body eliminate carcinogens before they harm our genes. A recent AICR-funded project by Dr. Wallig and his colleagues sought to find out what would be the effect of exposing phase 2 enzymes to these two phytochemicals simultaneously. They found that the two compounds performed better together to protect rats against liver cancer.

"If the effect of these two phytochemicals on activating phase 2 enzymes was simply additive, we would have gotten 2 + 2 = 4. But what we found was that 2 + 2 = more like 6," he says.

Dr. Wallig says exactly why synergy occurs between crambene and I3C is not understood, but scientists theorize that it's because I3C activates phase 2 enzymes by a mechanism known as the xenobiotic response element. ("Xenobiotic" means a substance that is foreign to the body). Crambene also activates phase 2 enzymes, but via a different mechanism - the antioxidant response element.

"Response elements are little pieces of DNA in the regulatory region of the gene," explains Dr. Wallig. "When they're under the appropriate stimulus, the response element gets activated and enhances expression of that gene," says Dr. Wallig. "I3C, by activating the xenobiotic response element, turns on one set of genes; crambene, via the antioxidant response element, turns on a whole other set of genes."

Although I3C's xenobiotic response element activates phase 2 enzymes, which are generally beneficial, it also activates phase 1 enzymes. "This can be something of a two-edged sword," says Dr. Wallig.

Phase 1 enzymes are also detoxifying enzymes. But at the same time they can activate precarcinogenic compounds, he notes. Crambene, however, does not affect phase 1 enzymes. That may be the reason why I3C and crambene work so well synergistically.

More Antioxidants for More Synergy

Although Dr. Wallig's work in lab rats showed that crambene and I3C produce a significant synergistic effect, the doses that were used to demonstrate a protective effect against liver cancer in animals could not be achieved in a human diet. He thinks that further experimentation with the addition of other antioxidants, such as vitamins C and E and selenium, might be able to create a cancer-protective treatment for humans.

In the meantime, his work clearly suggests the benefit of eating a wide variety of vegetables and fruits for the greatest possible synergistic effects.

Reference

Wallig M et al. Synergy among phytochemicals within crucifers: does it translate into chemoprevention? J Nutr. 2005;135(12S):2972S-7S. All active news articles
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