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Flower Power: Corn lily compound stops cancer in mice

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1:26pm, August 28, 2002
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The corn lily appears harmless enough. But when a pregnant ewe eats this mountain flower, she gives birth to lambs with grotesque birth defects, such as a missing eye. In 1968, researchers identified the chemical responsible for this damage and named it cyclopamine–for the one-eyed giant of Greek lore.

In recent years, scientists have tested cyclopamine to see whether its assault on the fast-growing cells of embryos and fetuses might be turned against tumor cells, which also multiply rapidly. A new study in mice suggests cyclopamine can inhibit medulloblastoma, a brain cancer in children.

Researchers at the Johns Hopkins Medical Institutions in Baltimore implanted human medulloblastoma cells under the skin of mice and then gave some of the animals injections of cyclopamine. The treatment stopped the cancer within a week, completely wiping it out in some animals. The drug showed no adverse effects.

In other experiments, scientists at the University of Washington in Seattle showed that medulloblastoma cells in a lab dish die in the presence of cyclopamine but that other brain cancer cells are unaffected by it.

The two teams report their findings in the Aug. 30 Science.

A series of molecular reactions, or pathway, signals a cell to grow in a fetus or newborn and later to slow down or stop growth. In medulloblastoma, at least one such pathway switches on inappropriately and signals cells to grow when they shouldn't, says study coauthor David M. Berman of Johns Hopkins.

Scientists first identified the growth-promoting pathway in fruit flies and named it hedgehog because disruptions in it give the insect's larvae a spiky appearance.

The hedgehog pathway caught the attention of cancer researchers when studies revealed that people with Gorlin's syndrome, a hereditary condition that leaves a person highly susceptible to medulloblastoma, often lack a protein that acts as a brake on the pathway, says Berman.

In the late 1990s, study coauthor Philip A. Beachy of Johns Hopkins found that mice with a genetically disrupted hedgehog pathway often have only one eye. The oddity was reminiscent of the birth defect in lambs exposed to cyclopamine before birth. This coincidence suggested that cyclopamine blocks the hedgehog pathway.

If so, the scientists reasoned, it might also stop tumor growth in which the pathway is overactive.

"The oncology field was presented with this wealth of genetic data" on the fruit fly's hedgehog pathway and is now putting it to use, says Tom Curran of St. Jude Children's Research Hospital in Memphis. While the roles of the genes and proteins guiding the chain of reactions are still being sorted out, targeting the pathway with cyclopamine shows promise, he says.

Matthew P. Scott of the Howard Hughes Medical Institute at Stanford University School of Medicine isn't surprised by the finding that cyclopamine doesn't work against other kinds of brain cancer. "It conveys once again that cancer is a lot of different diseases, and you have to go at them one at a time," he says.

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