Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease
| Autor: | Catherine Lombard, Seonho Ryu, Prakash S. Nagarkatti, Robert J. McKallip, Billy R. Martin, Steven Grant, Michael T. Fisher, Mitzi Nagarkatti |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Cannabinoid receptor Cell Survival medicine.drug_class Receptors Drug medicine.medical_treatment Immunology Drug Evaluation Preclinical Antineoplastic Agents Apoptosis Biology Ligands Biochemistry Jurkat cells Mice Immune system Tumor Cells Cultured Cannabinoid receptor type 2 medicine Animals Humans Dronabinol Receptors Cannabinoid Receptor Dose-Response Relationship Drug Cannabinoids Cell Biology Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia Lymphoid Mice Inbred C57BL Survival Rate Treatment Outcome Cancer research lipids (amino acids peptides and proteins) Cannabinoid |
| Zdroj: | Blood. 100:627-634 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2002-01-0098 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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