Cannabinoid Receptor Agonists Anti-Lymphoma Agents
Cannabinoid Receptor Agonists May Be Effective Anti-Lymphoma Agents
According to researchers at Virginia Commonwealth University in Richmond, Delta-9-tetrahydrocannibinol (THC), the major component of marijuana, and other cannabinoids induce apoptosis in murine tumors of immune origin.
Dr. Mitzi Nagarkatti explained in an interview with Reuters Health that cancers of the immune system like other cells express a cannabinoid receptor known as CB2. Compounds that bind CB2 receptors selectively induce apoptosis in these cancer cells, Nagarkatti said. Moreover, “compounds that interact with CB2 will not exhibit psychotropic effects.”
Dr. Nagarkatti and her colleagues in a series of in vitro experiments exposed murine lymphoma and mastocytoma cells to four cannabinoid receptor agonists. THC and two of the others significantly minimized cell viability and increased apoptosis. The effect of THC was confirmed by in vivo experiments. Cells collected from animals treated with the highest dose of THC showed 77.3% apoptosis ten days after mice were injected with lymphoma cells and two weeks of THC-treatment cured 25% of lymphoma-bearing mice.
“It is possible that the immunosuppressive effects of THC may have interfered with the host’s antitumor immunity, which may account for a lower percentage of cures,” the researchers commented. The research team is conducting murine dose-ranging studies. It was also demonstrated by the research group that three human leukemia and lymphoma cell lines expressed CB2 and not CB1. Three cannabinoids, including THC, induced apoptosis in these cell lines in vitro, and THC demonstrated the same effect when cultured with cells from patients diagnosed with acute lymphoblastic leukemia.
“Recently, however, we identified a human cell line that was resistant,” Dr. Nagarkatti’s team reports. “Further studies are in progress to address whether this cell line lacks physical or functional cannabinoid receptors and/or signaling molecules that trigger apoptosis.” In addition, the research team is “screening a large number of CB2 analogs to identify compounds that are highly efficacious in killing the cancer cells,” Dr. Nagarkatti said. “We are also investigating whether endogenous cannabinoids can exert antitumor activity.”