| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics |
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain [C. S., T. G. d. P., D. R., G. V., I. G-R., M. G.]; Neurodegeneration Group, Cajal Institute, CSIC, 28002 Madrid, Spain [M. L. d. C.]; Department of Pathology, Clínica Puerta de Hierro, 28035 Madrid, Spain [C. C., S. R. y C.]; and Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905 [J. W. H.]
The development of new therapeutic strategies is essential for the management of gliomas, one of the most malignant forms of cancer. We have shown previously that the growth of the rat glioma C6 cell line is inhibited by psychoactive cannabinoids (I. Galve-Roperh et al., Nat. Med., 6: 313–319, 2000). These compounds act on the brain and some other organs through the widely expressed CB1 receptor. By contrast, the other cannabinoid receptor subtype, the CB2 receptor, shows a much more restricted distribution and is absent from normal brain. Here we show that local administration of the selective CB2 agonist JWH-133 at 50 µg/day to Rag-2-/- mice induced a considerable regression of malignant tumors generated by inoculation of C6 glioma cells. The selective involvement of the CB2 receptor in this action was evidenced by: (a) the prevention by the CB2 antagonist SR144528 but not the CB1 antagonist SR141716; (b) the down-regulation of the CB2 receptor but not the CB1 receptor in the tumors; and (c) the absence of typical CB1-mediated psychotropic side effects. Cannabinoid receptor expression was subsequently examined in biopsies from human astrocytomas. A full 70% (26 of 37) of the human astrocytomas analyzed expressed significant levels of cannabinoid receptors. Of interest, the extent of CB2 receptor expression was directly related with tumor malignancy. In addition, the growth of grade IV human astrocytoma cells in Rag-2-/- mice was completely blocked by JWH-133 administration at 50 µg/day. Experiments carried out with C6 glioma cells in culture evidenced the internalization of the CB2 but not the CB1 receptor upon JWH-133 challenge and showed that selective activation of the CB2 receptor signaled apoptosis via enhanced ceramide synthesis de novo. These results support a therapeutic approach for the treatment of malignant gliomas devoid of psychotropic side effects.
This article has been cited by other articles:
|
|
 |
|
  C. Blazquez, M. Salazar, A. Carracedo, M. Lorente, A. Egia, L. Gonzalez-Feria, A. Haro, G. Velasco, and M. Guzman Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression Cancer Res., March 15, 2008; 68(6): 1945 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Munoz-Luque, J. Ros, G. Fernandez-Varo, S. Tugues, M. Morales-Ruiz, C. E. Alvarez, S. L. Friedman, V. Arroyo, and W. Jimenez Regression of Fibrosis after Chronic Stimulation of Cannabinoid CB2 Receptor in Cirrhotic Rats J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 475 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ramer and B. Hinz Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1 J Natl Cancer Inst, January 2, 2008; 100(1): 59 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bifulco, C. Grimaldi, P. Gazzerro, S. Pisanti, and A. Santoro Rimonabant: Just an Antiobesity Drug? Current Evidence on Its Pleiotropic Effects Mol. Pharmacol., June 1, 2007; 71(6): 1445 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. DeMorrow, S. Glaser, H. Francis, J. Venter, B. Vaculin, S. Vaculin, and G. Alpini Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth: RECRUITMENT OF Fas AND Fas LIGAND TO LIPID RAFTS J. Biol. Chem., April 27, 2007; 282(17): 13098 - 13113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Aguado, A. Carracedo, B. Julien, G. Velasco, G. Milman, R. Mechoulam, L. Alvarez, M. Guzman, and I. Galve-Roperh Cannabinoids Induce Glioma Stem-like Cell Differentiation and Inhibit Gliomagenesis J. Biol. Chem., March 2, 2007; 282(9): 6854 - 6862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. Sarfaraz, F. Afaq, V. M. Adhami, A. Malik, and H. Mukhtar Cannabinoid Receptor Agonist-induced Apoptosis of Human Prostate Cancer Cells LNCaP Proceeds through Sustained Activation of ERK1/2 Leading to G1 Cell Cycle Arrest J. Biol. Chem., December 22, 2006; 281(51): 39480 - 39491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Blazquez, A. Carracedo, L. Barrado, P. J. Real, J. L. Fernandez-Luna, G. Velasco, M. Malumbres, and M. Guzman Cannabinoid receptors as novel targets for the treatment of melanoma FASEB J, December 1, 2006; 20(14): 2633 - 2635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Palazuelos, T. Aguado, A. Egia, R. Mechoulam, M. Guzman, and I. Galve-Roperh Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation FASEB J, November 1, 2006; 20(13): 2405 - 2407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ligresti, A. S. Moriello, K. Starowicz, I. Matias, S. Pisanti, L. De Petrocellis, C. Laezza, G. Portella, M. Bifulco, and V. Di Marzo Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1375 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. McKallip, W. Jia, J. Schlomer, J. W. Warren, P. S. Nagarkatti, and M. Nagarkatti Cannabidiol-Induced Apoptosis in Human Leukemia Cells: A Novel Role of Cannabidiol in the Regulation of p22phox and Nox4 Expression Mol. Pharmacol., September 1, 2006; 70(3): 897 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Caffarel, D. Sarrio, J. Palacios, M. Guzman, and C. Sanchez {Delta}9-Tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells through Cdc2 Regulation. Cancer Res., July 1, 2006; 66(13): 6615 - 6621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Carracedo, M. Gironella, M. Lorente, S. Garcia, M. Guzman, G. Velasco, and J. L. Iovanna Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress-Related Genes. Cancer Res., July 1, 2006; 66(13): 6748 - 6755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. McKallip, M. Nagarkatti, and P. S. Nagarkatti {Delta}-9-Tetrahydrocannabinol Enhances Breast Cancer Growth and Metastasis by Suppression of the Antitumor Immune Response J. Immunol., March 15, 2005; 174(6): 3281 - 3289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Benito, W.-K. Kim, I. Chavarria, C. J. Hillard, K. Mackie, R. M. Tolon, K. Williams, and J. Romero A Glial Endogenous Cannabinoid System Is Upregulated in the Brains of Macaques with Simian Immunodeficiency Virus-Induced Encephalitis J. Neurosci., March 9, 2005; 25(10): 2530 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sarfaraz, F. Afaq, V. M. Adhami, and H. Mukhtar Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer Cancer Res., March 1, 2005; 65(5): 1635 - 1641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Ramirez, C. Blazquez, T. G. del Pulgar, M. Guzman, and M. L. de Ceballos Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation J. Neurosci., February 23, 2005; 25(8): 1904 - 1913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Powles, R. t. Poele, J. Shamash, T. Chaplin, D. Propper, S. Joel, T. Oliver, and W. M. Liu Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway Blood, February 1, 2005; 105(3): 1214 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. RODRIGUEZ de FONSECA, I. DEL ARCO, F. J. BERMUDEZ-SILVA, A. BILBAO, A. CIPPITELLI, and M. NAVARRO THE ENDOCANNABINOID SYSTEM: PHYSIOLOGY AND PHARMACOLOGY Alcohol Alcohol., January 1, 2005; 40(1): 2 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tegeder and G. Geisslinger Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications Pharmacol. Rev., September 1, 2004; 56(3): 351 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Blazquez, L. Gonzalez-Feria, L. Alvarez, A. Haro, M. L. Casanova, and M. Guzman Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas Cancer Res., August 15, 2004; 64(16): 5617 - 5623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Massi, A. Vaccani, S. Ceruti, A. Colombo, M. P. Abbracchio, and D. Parolaro Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 838 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Di Filippo, F. Rossi, S. Rossi, and M. D'Amico Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN J. Leukoc. Biol., March 1, 2004; 75(3): 453 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Klein, C. Newton, K. Larsen, L. Lu, I. Perkins, L. Nong, and H. Friedman The cannabinoid system and immune modulation J. Leukoc. Biol., October 1, 2003; 74(4): 486 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maccarrone, S. Cecconi, G. Rossi, N. Battista, R. Pauselli, and A. Finazzi-Agro Anandamide Activity and Degradation Are Regulated by Early Postnatal Aging and Follicle-Stimulating Hormone in Mouse Sertoli Cells Endocrinology, January 1, 2003; 144(1): 20 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Anikwue, J. W. Huffman, Z. L. Martin, and S. P. Welch Decrease in Efficacy and Potency of Nonsteroidal Anti-Inflammatory Drugs by Chronic Delta 9-Tetrahydrocannabinol Administration J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 340 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gomez del Pulgar, M. L. de Ceballos, M. Guzman, and G. Velasco Cannabinoids Protect Astrocytes from Ceramide-induced Apoptosis through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway J. Biol. Chem., September 20, 2002; 277(39): 36527 - 36533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. McKallip, C. Lombard, M. Fisher, B. R. Martin, S. Ryu, S. Grant, P. S. Nagarkatti, and M. Nagarkatti Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease Blood, June 28, 2002; 100(2): 627 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Fathallah-Shaykh Darts in the Dark Cure Animal, but Not Human, Brain Tumors Arch Neurol, May 1, 2002; 59(5): 721 - 724. [Full Text] [PDF]
|
|
|
|
|
|
S. O. P. Jacobsson, T. Wallin, and C. J. Fowler Inhibition of Rat C6 Glioma Cell Proliferation by Endogenous and Synthetic Cannabinoids. Relative Involvement of Cannabinoid and Vanilloid Receptors J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 951 - 959. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
