Plant compound kills brain tumor cells

A chemical isolated from a weed that grows in mountain meadows in the western United States kills the cells of an aggressive brain cancer that affects some children. The compound, cyclopamine, blocks a signaling pathway that appears to be important for the survival of medulloblastoma, a form of cancer for which there is no effective treatment.

In an article published in the August 30, 2002, issue of the journal Science, a research team led by Howard Hughes Medical Institute investigator Philip A. Beachy reported that cyclopamine effectively killed cultured mouse medulloblastoma cells and tumors implanted in animals, as well as medulloblastoma cells extracted from human tumors.

"It will be difficult to obtain sufficient quantities of cyclopamine, since it must be extracted and purified from the plant source, Veratrum californicum, the corn lily," said Beachy, who is at The Johns Hopkins University School of Medicine. "However, we believe that with this study, the evidence is in place to justify an effort to develop a supply so that it can be tested in humans." Beachy and his colleagues at Johns Hopkins collaborated with researchers from the Fred Hutchinson Cancer Research Center and the University of Washington/Children's Hospital in Seattle.

Beachy said there are some parallels between cyclopamine and taxol, a drug used to treat breast cancer drug that was initially in short supply because it had to be isolated from the bark of the Pacific yew tree. However, as taxol proved clinically effective, researchers developed an alternate method of partial synthesis of the compound from a more plentiful precursor in the needles that made the drug available in sufficient supply.

Beachy and his colleagues began to explore whether cyclopamine would be effective against medulloblastoma after studies by several groups, including HHMI investigator Matthew Scott and his

Contact: Jim Keeley
Howard Hughes Medical Institute

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