Cyclopamine, derived from the corn lily may treat and prevent basal cell carcinoma

Researchers at the University of Texas Medical Branch at Galveston (UTMB) have demonstrated in laboratory animals that a compound derived from a common plant can be used to treat and prevent the most widespread form of cancer in people— the first such therapy to succeed in an experimental animal and one that may lead to therapies in people for this and other frequently encountered cancers.

The scientists reported in the Oct. 15, 2004, issue of Cancer Research that oral administration of cyclopamine dramatically reduced tumor development in mice genetically engineered to be prone to the skin cancer known as basal cell carcinoma (BCC) when exposed to ultraviolet light. Cyclopamine is derived from the corn lily, a weed-like plant that grows in mountain meadows in the western United States.

The most common of all human cancers, BCC afflicts 800,000 Americans each year, according to the Skin Cancer Foundation. One of every three new cancers is a skin cancer, it says, and the vast majority are basal cell carcinomas.

“We showed 90 percent fewer microscopic BCC tumors after treating with cyclopamine, and 50 percent fewer visible tumors,” said the study’s lead author, Jingwu Xie, an assistant professor of pharmacology and toxicology at UTMB and scientist in the university’s Sealy Center for Cancer Cell Biology. “Based on the microscopic tumor results, we see a potential to prevent new tumors from developing, while the visible tumor reduction shows us that this can be used for treatment. And since there’s no noticeable toxicity to mice, this therapy has great clinical promise.”

Because cyclopamine kills tumor cells by breaking only a single link in the chain of biochemical reactions leading to cancer— known to scientists as the “hedgehog pathway”— it should have far fewer side effects than more traditional chemotherapies, Xie said. (“Hedgehog” is a signaling protein important to animal growth and development that takes its name from the spiky appearance of fruit flies that lack the gene to produce it.) The hedgehog pathway has also been implicated in prostate cancer, brain tumors, lung cancer and some types of breast cancer, leading Xie and other researchers to believe that a compound like cyclopamine that shuts down hedgehog could serve as a weapon against many different kinds of cancer. (A paper by Xie examining the role of the hedgehog pathway in prostate cancer and describing the ability of cyclopamine to kill prostate cancer cells in test-tube experiments appeared this week in the online journal Molecular Cancer and can be found at http://www.molecular-cancer.com/home/ .)

According to Xie, cyclopamine’s safety and effectiveness against BCC tumors when given orally boost hopes that it could find wider clinical applications. “We used drinking water to deliver the drug to the mice, and from drinking water to the circulatory system to the skin there are a lot of barriers,” Xie said. “If you can treat skin tumors with an orally administered drug, you should be able to treat other kinds of tumor, too — gastrointestinal tumors, prostate cancers, lung cancers and some breast cancers.”

The UTMB team collaborated on the research with scientists from Columbia University, the National Cancer Institute in Bethesda, Md., the University of California at San Francisco and the University of Texas Health Science Center at Houston .The paper, “Inhibition of Smoothened Signaling Prevents Ultraviolet B-induced Basal Cell Carcinomas through Regulation of Fas Expression and Apoptosis,” can be found online at http://cancerres.aacrjournals.org/ .

http://www.utmb.edu/