Health & Medical Cancer & Oncology

Do Lilies Hold Clues to Cancer?

Do Lilies Hold Clues to Cancer?

Do Lilies Hold Clues to Cancer?

Aug. 30, 2000 -- What do corn lilies, one-eyed sheep, and Sonic hedgehog have in common?

Clues to the mystery of what causes skin and other cancers, and possible strategies to control them, according to research reported in the Aug. 31 issue of the scientific journal Nature.

The mystery begins in a pasture where pregnant sheep show no signs of being sick themselves, but give birth to lambs with a severe brain defect and only a single, centrally placed eye -- reminiscent of the mythological creature Cyclops.

Agricultural scientists discovered that the mothers of the deformed lambs grazed on corn lilies while they were pregnant. Biochemists then deduced that cyclopamine, a chemical found in the lily plant, is the culprit. Developmental biologists figured out why: the cyclopamine turns off the so-called Sonic hedgehog pathway, a chain reaction of proteins sending signals to each other, giving the complex instructions the embryo needs to develop normally.

So what does this have to do with cancer? Many genes needed for normal development in the embryo turn off in the adult, but can cause cancer if they are turned on again. And the Sonic hedgehog pathway is controlled by genes found to be important in embryonic development, as well as in certain tumors affecting the skin and brain of adult humans.

Fitting the last puzzle piece into place, researchers at Johns Hopkins and Stanford Universities guessed that if cyclopamine turns off genes needed for embryonic development, it might do the same in cancer cells, shutting down the Sonic hedgehog pathway and stopping their uncontrolled growth.

Genes that control the Sonic hedgehog pathway have been linked to different human tumors, especially the very common form of skin cancer called basal cell carcinoma. This cancer usually appears in sun-exposed areas in fair-skinned people over age 40. While not lethal because of its slow growth and lack of spread to internal organs, it does invade surrounding tissue, sometimes requiring disfiguring surgery to treat it completely.

Cells from basal cell carcinoma are difficult to grow in the laboratory. So the Hopkins researchers did the next best thing -- they tested mouse cells with gene mutations similar to those seen in the skin cancer. Cyclopamine appeared to stop the growth of these cells, and even to reverse some of their malignant characteristics. Next, the researchers designed chemicals that were similar to cyclopamine, but even better at stopping growth of the cancer-like cells.

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