J Pharmacol Exp Ther. 2009 Nov 4. [Epub ahead of print]
Antitumorigenic effects of cannabinoids beyond apoptosis.
Freimuth N,
Ramer R,
Hinz B.
University of Rostock.
According to the World Health Organization the cases of death caused by cancer will have been doubled until the year 2030. By 2010 cancer is expected to be the cause of death number one. It is therefore necessary to explore novel approaches for the treatment of cancer. During past years the antitumorigenic effects of cannabinoids have emerged as an exciting field in cancer research. Apart from their proapoptotic and antiproliferative action, recent research has shown that cannabinoids
may likewise affect tumor cell angiogenesis, migration, invasion, adhesion and metastasation. This review will summarize the data concerning the influence of cannabinoids on these locomotive processes beyond modulation of cancer cell apoptosis and proliferation. The findings discussed here provide a new perspective on the antitumorigenic potential of cannabinoids.
PMID: 19889794 [PubMed - as supplied by publisher]
Mol Cancer Ther. 2009 Nov 3. [Epub ahead of print]
Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer.
Qamri Z,
Preet A,
Nasser MW,
Bass CE,
Leone G,
Barsky SH,
Ganju RK.
1Department of Pathology, The Ohio State University College of Medicine, 2Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine and Public Health, Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio; 3Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; 4Lombardi Comprehensive Cancer Center, Washington, District of Columbia; and 5Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard Winston-Salem, North Carolina.
Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis. [Mol Cancer Ther 2009;8(11):3117-29].