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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 severalvarieties 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.

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References1. 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 inglioblastoma cellsAuthor Affiliations

1. 1 Laboratoire de Toxicologie and 2 Laboratoire 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; 6 Department of Neurosurgery,Wagner Jaureg Hospital, Linz, Austria; and 7 Institute of Cancer Research,

Department of Medicine I, Medical University of Vienna, Vienna, Austria1. Requests for reprints:

Robert Kiss, Laboratoire de Toxicologie, Institut de Pharmacie, Universit Librede 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

Abstract

mailto:rkiss@ulb.ac.bemailto:rkiss@ulb.ac.be

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Cell motility and resistance to apoptosis characterize glioblastoma multiforme growthand malignancy. Narciclasine, a plant growth modulator, could represent a powerful newweapon 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 beendetermined in models of human glioblastoma multiforme. Narciclasine impairsglioblastoma multiforme growth by markedly decreasing mitotic rates without inducingapoptosis. The compound also modulates the Rho/Rho kinase/LIM kinase/cofilinsignaling pathway, greatly increasing GTPase RhoA activity as well as inducing actinstress fiber formation in a RhoA-dependent manner. Lastly, the treatment of humanglioblastoma 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 highesttherapeutic benefits in treating glioblastoma multiforme patients. Our results show for thefirst time that narciclasine, a plant growth modulator, activates Rho and stress fibers in

glioblastoma multiforme cells and significantly increases the survival of humanglioblastoma multiforme preclinical models. This statement is made despite therecognition 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 oncologywithin a three to four year period in order to help patients with brain cancers, includinggliomas, as well as brain metastases," said Robert Kiss, co-author of the study from theLaboratory of Toxicology at the Institute of Pharmacy at the Universit Libre deBruxelles in Brussels, Belgium.

"We hope narciclasine could be given to brain cancer patients in addition to conventionaltherapies."

To make this discovery, Kiss and colleagues used computer-assisted techniques toidentify targets for narciclasine in cancer cells. The strongest potential candidate toemerge 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 significantlylonger when treated with narciclasine than those mice left untreated. The researchers

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believe that narciclasine selectively inhibits the proliferation of very aggressive cancer cells, while avoiding adverse effects on normal cells. Narciclasine could be used in thenear 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-in-Chief of The FASEB Journal .

"It doesn't mean that you should eat daisies or daffodils for what ails you, but that modernmedicinal chemistry can pluck new chemicals from stuff that grows in the garden. This isa good one!"

A new research study has been published in the November 2010 print issue of TheFASEB Journal .

Read more: Daffodils harbour brain cancer cure - The Times of Indiahttp://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbour- brain-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 foundin 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] offershope 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 oncologywithin a three to four year period in order to help patients with brain cancers, includinggliomas, as well as brain metastases," said Robert Kiss, Ph.D., co-author of the studyfrom 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 toidentify targets for narciclasine in cancer cells. The strongest potential candidate toemerge was the eEF1A elongation factor. Researchers then grafted human melanoma

brain metastatic cells into the brains of genetically altered mice. Results showed that theinjected mice survived significantly longer when treated with narciclasine than those

http://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbour-brain-cancer-cure/articleshow/6858950.cms#ixzz14C1McXkghttp://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbour-brain-cancer-cure/articleshow/6858950.cms#ixzz14C1McXkghttp://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbour-brain-cancer-cure/articleshow/6858950.cms#ixzz14C1McXkghttp://timesofindia.indiatimes.com/life-style/health-fitness/health/Daffodils-harbour-brain-cancer-cure/articleshow/6858950.cms#ixzz14C1McXkg

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mice left untreated. The researchers believe that narciclasine selectively inhibits the proliferation of very aggressive cancer cells, while avoiding adverse effects on normalcells. 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 newchemicals 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 largestcoalition of biomedical research associations in the United States. FASEB enhances theability 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.

Notes:

Gwendoline Van Goietsenoven, Jenna Hutton, Jean-Paul Becker, Benjamin Lallemand,Francis Robert, Florence Lefranc, Christine Pirker, Guy Vandenbussche, Pierre VanAntwerpen, Antonio Evidente, Walter Berger, Martine Prvost, Jerry Pelletier, RobertKiss, Terri Goss Kinzy, Alexander Kornienko and Vronique Mathieu:

Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combatmelanomas.

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