MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on March 29, 2006; DOI: 10.1124/mol.105.021089

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.105.021089v1
70/1/51    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kogan, N. M
Right arrow Articles by Mechoulam, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kogan, N. M
Right arrow Articles by Mechoulam, R.


Received for publication November 30, 2005.
Revised March 20, 2006.
Accepted for publication March 21, 2006.

A Cannabinoid Quinone Inhibits Angiogenesis by Targeting Vascular Endothelial Cells

Natalya M Kogan 1*, Cristina Blazquez 2, Luis Alvarez 3, Ruth Gallily 1, Michael Schlesinger 1, Manuel Guzman 2, Raphael Mechoulam 4

1 Hebrew University, Jerusalem 2 Complutense University, Madrid 3 La Paz University Hospital, Madrid 4 Hebrew University

* Address correspondence to: E-mail: natalya{at}md.huji.ac.il

Abstract

Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compounds a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, HU-331, is highly effective against tumor xenografts in nude mice. For evaluation of the anti-angiogenic action of cannabinoid quinones collagen-embedded rat aortic rings assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells human cDNA microarrays were used. Immunostaining with anti-CD31 of tumors grown in nude mice served to indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly anti-angiogenic, significantly inhibiting both basal and tumor angiogenesis at concentrations as low as 300 nM. HU-331 inhibits angiogenesis by directly inducing apoptosis of vascular endothelial cells without changing the expression of pro- and anti-angiogenic cytokines and their receptors. A significant decrease in the total area occupied by vessels in HU-331-treated tumors was seen. On the basis of these data we consider HU- 331 to have high potential as a new anti-angiogenic and anticancer drug.


Key words: Cannabinoid, Apoptosis, Angiogenesis


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
N. M. Kogan, M. Schlesinger, M. Peters, G. Marincheva, R. Beeri, and R. Mechoulam
A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study
J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 646 - 653.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. M. Kogan, M. Schlesinger, E. Priel, R. Rabinowitz, E. Berenshtein, M. Chevion, and R. Mechoulam
HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor
Mol. Cancer Ther., January 1, 2007; 6(1): 173 - 183.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics