Cannabinoid Receptor Agonists May Be Novel Class of
Publication date: July 25, 2002
Author: Faith Reidenbach
NEW YORK (Reuters Health) Jul 25 - Delta-9-tetrahydrocannibinol (THC), the major component of marijuana, and other cannabinoids induce apoptosis in murine tumors of immune origin, according to researchers at Virginia Commonwealth University in Richmond.
Like other immune cells, cancers of the immune system express a cannabinoid receptor known as CB2, Dr. Mitzi Nagarkatti explained in an interview with Reuters Health. Compounds that bind CB2 receptors selectively induce apoptosis in these cancer cells, she said. Moreover, "compounds that interact with CB2 will not exhibit psychotropic effects."
In a series of in vitro experiments, Dr. Nagarkatti and her colleagues exposed murine lymphoma and mastocytoma cells to four cannabinoid receptor agonists. THC and two of the others significantly reduced cell viability and increased apoptosis, they report in the July 15th issue of Blood.
In vivo experiments confirmed the effect of THC. Ten days after mice were injected with lymphoma cells, cells collected from animals treated with the highest dose of THC showed 77.3% apoptosis. 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 comment. They are currently conducting murine dose-ranging studies.
The research group also demonstrated 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 showed 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 currently "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."
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