Letters to Nature Nature 213, 595 - 596 (11 February 1967); doi:10.

1038/213595a0 Narciclasine: an Antimitotic Substance from Narcissus Bulbs G. CERIOTTI Centro Studio Tumori, Busto Arsizio, Italy. A SYSTEMIC research programme for the detection of eventual antigrowth factors in plant extracts revealed a potent antimitotic substance which was isolated from several varieties of Narcissus bulbs. The substance was called "narciclasine". Antitumour activity was observed by Fitzgerald et al. 1, who used crude preparations of Narcissus bulbs. They found that pure alkaloids from the same source appeared to be inactive. -----------------References 1. Fitzgerald, D. B., Hartwell, J. L., and Leiter, J., J. Nat. Cancer Inst., 20, 763 (1958). | PubMed | ISI | ChemPort | 2. Ceriotti, G., Giorn. Botan., 73, 139 (1966). 3. Piozzi, F., Fuganti, C., Mandelli, R., and Ceriotti, G., Tetrahedron Lett., (in the press).

Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells
Author Affiliations Laboratoire de Toxicologie and 2Laboratoire de Chimie Bioanalytique, Toxicologie et Chimie Physique Applique, Institut de Pharmacie; 3Service de Neurochirurgie and 4Service d'Anatomie Pathologique, Hpital Erasme; 5 Laboratory of Image Analysis and Synthesis, Faculty of Applied Sciences, Universit Libre de Bruxelles, Brussels, Belgium; 6Department of Neurosurgery, Wagner Jaureg Hospital, Linz, Austria; and 7Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria 1. Requests for reprints: Robert Kiss, Laboratoire de Toxicologie, Institut de Pharmacie, Universit Libre de Bruxelles, Campus de la Plaine, Boulevard du Triomphe, 1050 Brussels, Belgium. Phone: 32-477-62-20-83; Fax: 322-332-53-35. E-mail: rkiss@ulb.ac.be 1.
1

Abstract

Cell motility and resistance to apoptosis characterize glioblastoma multiforme growth and malignancy. Narciclasine, a plant growth modulator, could represent a powerful new weapon targeting the Achilles' heel of glioblastoma multiforme and may offer the potential to better combat these devastating malignancies. The in vitro effects of narciclasine on cell proliferation, morphology, actin cytoskeleton organization, and the Rho/Rho kinase/LIM kinase/cofilin pathway and its antitumor activity in vivo have been determined in models of human glioblastoma multiforme. Narciclasine impairs glioblastoma multiforme growth by markedly decreasing mitotic rates without inducing apoptosis. The compound also modulates the Rho/Rho kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner. Lastly, the treatment of human glioblastoma multiforme orthotopic xenograft- bearing mice with nontoxic doses of narciclasine significantly increased their survival. Narciclasine antitumor effects were of the same magnitude as those of temozolomide, the drug associated with the highest therapeutic benefits in treating glioblastoma multiforme patients. Our results show for the first time that narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma multiforme cells and significantly increases the survival of human glioblastoma multiforme preclinical models. This statement is made despite the recognition that to date, irrespective of treatment, no single glioblastoma multiforme patient has been cured. [Mol Cancer Ther 2009;8(7):173950]

DAFFODILS HARBOUR BRAIN CANCER CURE ANI, Nov 2, 2010, 03.08pm IST Scientists have discovered narciclasine, a natural compound found in daffodil bulbs, 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, co-author of the study from the Laboratory of Toxicology at the Institute of Pharmacy at the Universit 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, Editor-inChief 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!" A new research study has been published in the November 2010 print issue of The FASEB Journal . Read more: Daffodils harbour brain cancer cure - The Times of India http://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbourbrain-cancer-cure/articleshow/6858950.cms#ixzz14C1McXkg

Narciclasine Scientists turn a new leaf to discover a compound in daffodils that targets brain cancer. New research in the FASEB Journal suggests that narciclasine, a natural compound found in daffodil bulbs, markedly reduces cancer cell proliferation and migration. 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 [see below] 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 Universit 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!" 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, wellbeing 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. Notes: 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 Prvost, Jerry Pelletier, Robert Kiss, Terri Goss Kinzy, Alexander Kornienko and Vronique Mathieu: Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas. In: The FASEB Journal; vol. 24 no. 11 4575-4584; published online before print July 19, 2010 DOI: 10.1096/fj.10-162263 URL: direct link Source: Federation of American Societies for Experimental Biology, FASEB