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Cannabinoid Receptor Agonists May Be Novel Class of Anti-Lymphoma Agents

Faith Reidenbach

Reuters Health

Thursday 25 Jul 2002

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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."

Blood 2002;100:627-634.



 

 

 

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