Faculty Collaboration Database

Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther 2009 Nov;8(11):3117-29

Date

11/06/2009

Pubmed ID

19887554

Pubmed Central ID

PMC4128286

DOI

10.1158/1535-7163.MCT-09-0448

Scopus ID

2-s2.0-70949091684 (requires institutional sign-in at Scopus site)   193 Citations

Abstract

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.

Author List

Qamri Z, Preet A, Nasser MW, Bass CE, Leone G, Barsky SH, Ganju RK

Author

Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Benzoxazines
Breast Neoplasms
Cannabinoids
Cell Cycle
Cell Growth Processes
Cell Line, Tumor
Cell Movement
Cyclooxygenase 2
Dinoprostone
Female
Humans
Immunohistochemistry
Lung Neoplasms
Male
Mammary Neoplasms, Experimental
Mice
Mice, Inbred C3H
Mice, SCID
Mice, Transgenic
Microscopy, Confocal
Morpholines
Naphthalenes
Neoplasm Metastasis
Neovascularization, Pathologic
RNA, Small Interfering
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Signal Transduction
Transfection
Xenograft Model Antitumor Assays