Related Experiment Videos
Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease
Robert J McKallip1, Catherine Lombard, Michael Fisher
1Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract:
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.
Insights
Cannabinoid receptor 2 (CB2) agonists induce apoptosis in immune-origin tumors. CB2 agonists show potential as novel anticancer agents, selectively targeting and killing immune system malignancies without psychotropic effects.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- The role of cannabinoid receptors in cancer therapy is an emerging area of research.
- CB2 receptors are implicated in immune system functions and are expressed on various immune cells.
Purpose of the Study:
- To investigate the potential of CB2 receptor ligation in inducing apoptosis in immune-origin tumors.
- To evaluate CB2 agonists as a therapeutic strategy for treating cancers of immune origin.
Main Methods:
- In vitro exposure of murine tumor cell lines (EL-4, LSA, P815) and human leukemia/lymphoma cell lines to cannabinoids (THC, HU-210, anandamide, JWH-015).
- In vivo treatment of EL-4 tumor-bearing mice with THC.
- Assessment of cell viability, apoptosis induction, tumor load, and survival rates.
- Analysis of CB1 and CB2 receptor expression in human tumor cells.
- Reversal studies using CB2 antagonist SR144528.
Main Results:
- delta-9-tetrahydrocannabinol (THC) and other CB2 agonists significantly reduced viability and induced apoptosis in murine and human immune-origin tumor cells.
- In vivo administration of THC reduced tumor load, increased apoptosis, and improved survival in tumor-bearing mice.
- Human leukemia and lymphoma cell lines expressed CB2 receptors and were susceptible to CB2 agonist-induced apoptosis, partially mediated by CB2 receptors.
Conclusions:
- CB2 cannabinoid receptors are potential therapeutic targets for inducing apoptosis in immune system malignancies.
- CB2 agonists, lacking psychotropic effects, represent promising novel anticancer agents for selective targeting of immune-origin tumors.