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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0098. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-01-0098v1 100/2/627    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McKallip, R. J. Articles by Nagarkatti, M. Search for Related Content PubMed PubMed Citation Articles by McKallip, R. J. Articles by Nagarkatti, M. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2002, Vol. 100, No. 2, pp. 627-634 NEOPLASIA Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease Robert J. McKallip, Catherine Lombard, Michael Fisher, Billy R. Martin, Seongho Ryu, Steven Grant, Prakash S. Nagarkatti, and Mitzi Nagarkatti From the Departments of Microbiology and Immunology, Pharmacology and Toxicology, and Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond. In the current study, we examined whether ligation of CB2 receptors would lead to induction of apoptosis in tumors of immune origin and whether CB2 agonist could be used to treat such cancers. Exposure of murine tumors EL-4, LSA, and P815 to delta-9-tetrahydrocannabinol (THC) in vitro led to a significant reduction in cell viability and an increase in apoptosis. Exposure of EL-4 tumor cells to the synthetic cannabinoid HU-210 and the endogenous cannabinoid anandamide led to significant induction of apoptosis, whereas exposure to WIN55212 was not effective. Treatment of EL-4 tumor-bearing mice with THC in vivo led to a significant reduction in tumor load, increase in tumor-cell apoptosis, and increase in survival of tumor-bearing mice. Examination of a number of human leukemia and lymphoma cell lines, including Jurkat, Molt-4, and Sup-T1, revealed that they expressed CB2 receptors but not CB1. These human tumor cells were also susceptible to apoptosis induced by THC, HU-210, anandamide, and the CB2-selective agonist JWH-015. This effect was mediated at least in part through the CB2 receptors because pretreatment with the CB2 antagonist SR144528 partially reversed the THC-induced apoptosis. Culture of primary acute lymphoblastic leukemia cells with THC in vitro reduced cell viability and induced apoptosis. Together, the current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis. Also, because CB2 agonists lack psychotropic effects, they may serve as novel anticancer agents to selectively target and kill tumors of immune origin. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Freimuth, R. Ramer, and B. Hinz Antitumorigenic Effects of Cannabinoids beyond Apoptosis J. Pharmacol. Exp. Ther., February 1, 2010; 332(2): 336 - 344. [Abstract] [Full Text] [PDF] H. Yin, A. Chu, W. Li, B. Wang, F. Shelton, F. Otero, D. G. Nguyen, J. S. Caldwell, and Y. A. Chen Lipid G Protein-coupled Receptor Ligand Identification Using {beta}-Arrestin PathHunterTM Assay J. Biol. Chem., May 1, 2009; 284(18): 12328 - 12338. [Abstract] [Full Text] [PDF] F. Cianchi, L. Papucci, N. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020