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Anti-cancer trigger revealed in broccoli

Something in broccoli may help prevent cancer—that much is part of the popular consciousness. But how the bushy-headed vegetable actually gets the job done is poorly understood.

Now, thanks to "gene chip" technology scientists have more than just seeds to work with. Researchers have identified scores of genes switched on by one of the most potent anti-cancer ingredients in cabbages and other vegetables, a molecule called sulforaphane.

The study is the first to employ gene chips to understand how a cancer-preventing agent works—though it will doubtless not be the last.

Shyam Biswal, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, led the study. He believes gene chips will increasingly be used to hunt for compounds—both natural and synthetic—that may help the body prevent tumors.

Sulforaphane, which has shown promise in warding off colon and lung cancers, apparently acts on a gene called Nrf2 (for nuclear factor E2 p45-related factor) that regulates an orchestra of other genes. These genes—their number is not known—police damaged or mutated cells.

The researchers gave sulforaphane to normal mice and a strain engineered to lack Nrf2. In the unaltered animals, a complex network of genes and proteins involved in ridding the body of carcinogens sprang into action. These included glutathione, a powerful anti-oxidant, and UGT, which helps detoxify cells.

"We do have an inherent system that can protect us [from tumors], but that system doesn't function so effectively," Biswal added. Priming it with substances like sulforaphane may help it perform better.

The Hopkins team will now use their approach to pit sulforaphane-like molecules against the real thing to see if they can find even more powerful molecules.

Without genomic tools, this study would have been impossibly time-consuming. "There are so many pathways which are getting activated, and many genes form a pathway," says Biswal. "It's a complex network." The findings appeared in Cancer Research.

John Hayes, a tumor expert at the University of Dundee in Scotland who studies Nrf2, notes that the Hopkins research helps define how the gene works. "There are multiple defense mechanisms under the control of this gene," he says, and no one had been able to illuminate the whole picture before.

Future studies of Nrf2 will need to examine what it does in the absence of cancer-preventing chemicals. "There is a complexity that we're struggling to understand," he says.

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Thimmulappa, R.K. et al. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62, 5196-5203 (September 15, 2002).

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