Cannabinoid Receptor Agonists May Be Novel Class of Anti-Lymphoma Agents
Cannabinoid Receptor Agonists May Be Novel Class of Anti-Lymphoma
Agents
By 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."
Blood 2002;100:627-634.
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