Scientists turn a new leaf to discover a compound in daffodils that targets brain cancer

(Press-News.org) When looking for new ways to treat aggressive brain cancers, an international team of scientists turned a new leaf and "discovered" the lowly daffodil. A new research study published in the November 2010 print issue of The FASEB Journal (http://www.fasebj.org) offers hope that a natural compound found in daffodil bulbs, called narciclasine, may be a powerful therapeutic against biologically aggressive forms of human brain cancers.

"We are planning to move a narciclasine derivative toward clinical trials in oncology within a three to four year period in order to help patients with brain cancers, including gliomas, as well as brain metastases," said Robert Kiss, Ph.D., co-author of the study from the Laboratory of Toxicology at the Institute of Pharmacy at the Université Libre de Bruxelles in Brussels, Belgium. "We hope narciclasine could be given to brain cancer patients in addition to conventional therapies."

To make this discovery, Kiss and colleagues used computer-assisted techniques to identify targets for narciclasine in cancer cells. The strongest potential candidate to emerge was the eEF1A elongation factor. Researchers then grafted human melanoma brain metastatic cells into the brains of genetically altered mice. Results showed that the injected mice survived significantly longer when treated with narciclasine than those mice left untreated. The researchers believe that narciclasine selectively inhibits the proliferation of very aggressive cancer cells, while avoiding adverse effects on normal cells. Narciclasine could be used in the near future to combat brain cancers, including gliomas, and metastases such as melanoma brain metastases.

"Scientists have been digging in odd corners to find effective treatments for brain cancer for decades, and now they've found one in daffodils." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "It doesn't mean that you should eat daisies or daffodils for what ails you, but that modern medicinal chemistry can pluck new chemicals from stuff that grows in the garden. This is a good one!"

### Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.

FASEB comprises 23 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve—through their research—the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Gwendoline Van Goietsenoven, Jenna Hutton, Jean-Paul Becker, Benjamin Lallemand, Francis Robert, Florence Lefranc, Christine Pirker, Guy Vandenbussche, Pierre Van Antwerpen, Antonio Evidente, Walter Berger, Martine Prévost, Jerry Pelletier, Robert Kiss, Terri Goss Kinzy, Alexander Kornienko, and Véronique Mathieu
Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas
FASEB J. 2010 24: 4575-4584. DOI: 10.1096/fj.10-162263 ; http://www.fasebj.org/cgi/content/abstract/24/11/4575