Veggies prevent cancer through key protein

Broccoli, cauliflower, and some of their relatives contain compounds that somehow boost the body’s defenses against DNA damage and cancer. Now, an international team of researchers has identified a crucial protein that helps these veggies exert their protective effect.

Many huge tumors formed in the stomach of a mouse (right) that lacked a protein researchers believe works with anticancer compounds in some vegetables. Fewer and smaller tumors formed in the stomach from a mouse that had the protein (left). Talalay

In earlier studies, researchers fed mice a diet rich in sulforaphane, a compound abundant in some vegetables of the genus Brassica. The animals produced increased quantities of so-called phase-2 enzymes, which mop up free radicals and other molecules that can harm DNA. When exposed to known carcinogens, the mice developed fewer cancers than a control group did, the researchers found.

A wide range of brassicas, including kale, brussels sprouts, and cabbage, contain sulforaphane (SN: 3/21/92, p. 183). Eating sprouts of these plants, particularly broccoli, yields large quantities of this compound (SN: 9/20/97, p. 183).

In the new study, researchers from Johns Hopkins University in Baltimore and Tsukuba University in Japan show that an anticancer compound similar to sulforaphane increases the production of phase-2 enzymes by triggering the release within a cell of a protein called nuclear respiratory factor-2, or Nrf2. The protein enters the cell nucleus and turns on a group of genes that produce the protective enzymes, says study coauthor Paul Talalay of Johns Hopkins. He adds that the protein could become a new target for designers of cancer-prevention drugs.

For the study, the Japanese researchers engineered mice that lack the gene that encodes Nrf2 and therefore can’t produce the protein. The Johns Hopkins scientists fed 20 of these mutant mice once a week for 4 weeks a high dose of a carcinogen found in cigarette smoke. They also fed 20 normal mice similar doses of the carcinogen.

After 30 weeks, the mutant mice had developed an average of 14 tumors in their stomachs, while the normal mice developed an average of 10. Moreover, each tumor in the mutant mice was roughly three times as large as one in the normal mice, says study coauthor Minerva Ramos-Gomez of Johns Hopkins. “There was no space to fill with food,” she recalls.

In another experiment, the Johns Hopkins researchers treated both groups of mice with the carcinogen along with the drug oltipraz. Like sulforaphane and its related compounds, this drug can raise the level of phase-2 enzymes and lower the risk of cancer.

After 30 weeks, the normal mice developed an average of only five tumors per mouse–half the number of their untreated counterparts–while the mutant mice without Nrf2 developed roughly as many tumors as their untreated counterparts.

Without Nrf2 to trigger the production of protective enzymes, even a diet rich in broccoli, cauliflower, or other foods that contain sulforaphane may not help prevent cancer, concludes nutritionist William G. Helferich of the University of Illinois at Urbana-Champaign. If there are people who lack Nrf2 protein, they may simply need to reduce their exposure to carcinogens, he adds. The researchers present their data in the March 13 Proceedings of the National Academy of Sciences.

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