Jewish World Review Aug. 30, 2002 / 22 Elul, 5762

Weed compound kills brain cancer cells

By Steve Mitchell | (UPI) A compound isolated from a weed appears to block a type of childhood brain cancer and show promise for treating other forms of the disease, a new study reveals.

Cyclopamine, a chemical found in the corn lily plant, has shrunk tumors in mice and killed human tumor cells in a test tube, Philip Beachy, lead author and professor of molecular biology and genetics at Johns Hopkins University, told United Press International.

"This is a positive indication that this type of approach may work in human tumors," he said. The corn lily plant grows wild in the western United States.

Ronald McKay, chief of the laboratory of molecular biology at the National Institute of Neurological Disorders and Stroke, told UPI, "I wouldn't say that we know that this is going to work in tumors in humans" but it definitely has potential.

The tumors used in the study came from a type of brain cancer called medullo-blastoma, the most common childhood brain cancer. McKay, who was not involved in the study, noted there are no effective treatments for medullo-blastoma, although surgical removal of the tumors sometimes can help.

A potential advantage of cyclopamine is it blocks a mechanism that is specific for cancer cells and thus is unlikely to affect normal, healthy cells, Beachy said. One of the problems with some cancer treatments such as chemotherapy and radiation is that they kill normal cells along with the cancer cells, which causes side effects such as hair loss, sores and diarrhea.

Beachy compared cyclopamine to Gleevec, a leukemia drug approved last year that blocks a specific protein and appears to carry fewer side effects than many other cancer drugs. "Gleevec is more specific for cancer and less toxic overall," he said.

Preliminary research with cyclopamine indicates it does not affect cells from other types of brain tumors or normal, healthy cells, suggesting it is very specific for medullo-blastoma tumor cells, Beachy said.

Beachy's team grew medullo-blastoma tumors and transplanted them to mice with weakened immune systems. Injection of cyclopamine directly into the tumor caused them to shrink. They then obtained human medullo-blastoma cells from patients who had their tumors surgically removed. Cyclopamine rapidly killed the tumor cells.

Cyclopamine got its name from the discovery several decades ago that pregnant sheep grazing on the plant gave birth to so-called Cyclops lambs with only one eye and other malformations, Beachy noted.

Further research determined that cyclopamine blocks a cellular process called the Hedgehog signaling pathway. This pathway is important for growth and development but if it becomes activated inappropriately due to mutation it can lead to cancers such as medullo-blastoma and basal cell carcinoma, the most common type of skin cancer.

Beachy said he "would love to see" the compound go into clinical trials to determine whether it is safe and effective in people. Johns Hopkins holds a patent on the compound and has licensed it to Curis, a Boston biotech company.

Curis Chief Scientific Officer Lee Rubin told UPI the company has "identified and synthesized much more potent molecules than cyclopamine that inhibit this pathway" when it is involved in medullo-blastoma and basal cell carcinoma. One of the advantages of synthesizing a compound is that it makes it cheaper to produce as a drug than purifying a compound from harvested plants.

Curis currently is testing the synthesized compounds in animals for their potential to treat basal cell carcinoma. So far the compounds appear safe and effective, Rubin said. The company currently is looking to partner with a pharmaceutical company with a dermatology focus and then to begin clinical trials in humans.

The research appears in the Aug. 30 issue of the journal Science.

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© 2002, United Press International