Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 16 April 2009, Vol. 113, No. 16, pp. 3781-3791.
Prepublished online as a Blood First Edition Paper on November 19, 2008; DOI 10.1182/blood-2008-09-177774.

This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Tables
Right arrow All Versions of this Article:
blood-2008-09-177774v1
113/16/3781    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ocio, E. M.
Right arrow Articles by Pandiella, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ocio, E. M.
Right arrow Articles by Pandiella, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Next Article next article arrow

Submitted September 8, 2008
Accepted November 10, 2008

Zalypsis: A novel marine-derived compound with potent antimyeloma activity that reveals high sensitivity of malignant plasma cells to DNA double strand breaks

Enrique M. Ocio*, Patricia Maiso, Xi Chen, Mercedes Garayoa, Stela Alvarez-Fernandez, Laura San-Segundo, David Vilanova, Lucia Lopez-Corral, Juan C. Montero, Teresa Hernandez-Iglesias, Enrique de Alava, Carlos Galmarini, Pablo Aviles, Carmen Cuevas, Jesus F. San-Miguel, and Atanasio Pandiella

Centro de Investigacion del Cancer, IBMCC/CSIC-Universidad de Salamanca, Salamanca, Spain
PharmaMar, Madrid, Spain
Hospital Universitario de Salamanca, Salamanca, Spain

* Corresponding author; email: emocio{at}usal.es.

Multiple Myeloma (MM) remains incurable, and new drugs with novel mechanisms of action are still needed. In this report, we have analyzed the action of Zalypsis, an alkaloid analogous to certain natural marine compounds, in MM. Zalypsis turned out to be the most potent antimyeloma agent we have tested so far, with IC50s from picomolar to low nanomolar ranges. It also showed remarkable ex vivo potency in plasma cells from patients and in MM cells in vivo xenografted in mice. Besides the induction of apoptosis and cell cycle arrest, Zalypsis provoked DNA double-strand-breaks (DSB), evidenced by an increase in phospho-Histone-H2AX and phospho-CHK2, followed by a striking overexpression of p53 in p53-wild type cell lines. In addition, in those cell lines in which p53 was mutated, Zalypsis also provoked DSB and induced cell death, although higher concentrations were required. Immunohistochemical studies in tumours also demonstrated Histone-H2AX phosphorylation and p53 overexpression. Gene expression profile studies were concordant with these results, revealing an important deregulation of genes involved in DNA-damage response. The potent in vitro and in vivo antimyeloma activity of Zalypsis uncovers the high sensitivity of tumour plasma cells to DSB, and strongly supports the use of this compound in MM patients.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020