Researchers show that nitric oxide-donating naproxen can boost colorectal cancer prevention
WASHINGTON, D.C. (April 21, 2010
)––Past randomized clinical trials
have shown that non-steroidal anti-inflammatory drugs (NSAIDs),
including naproxen, can reduce the risk of colon cancer and
precancerous polyps in humans
. Now, researchers at Fox Chase Cancer
Center have found that an investigational form of naproxen, called
nitric oxide-donating naproxen (NO-naproxen), can block one of the
earliest molecular changes that lead to colorectal cancer development
while also reducing gastrointestinal toxicity, a relatively common side
effect associated with NSAIDs.
"It appears that the
investigational form of naproxen we studied may be more effective than
standard naproxen in inhibiting colorectal tumor development," says
Margie Clapper, Ph.D., Co-Leader of the Cancer Prevention and Control
Program at Fox Chase Cancer Center. "An added benefit would be the
reduced gastrointestinal toxicity of this novel type of naproxen."
Clapper's group will present the new data at the 2010 annual meeting of
the American Association for Cancer Research.
"This new form
of naproxen is probably more protective because it blocks one of the
first steps in the colorectal cancer-causing pathway," she says.
work from Clapper and others has shown that increased activity of the
WNT/-catenin pathway is one of the earliest events in colorectal
cancer formation. To test whether NO-naproxen could reduce activation
of the pathway, the team used colon cancer cells that become
bioluminescent when the WNT/-catenin pathway is active. They found
that cells treated with NO-naproxen had about 50% less bioluminescence
than cells treated with naproxen.
"The major and novel
finding from the study is that the NO-naproxen can alter a particular
signaling pathway that is one of the earliest events in colon cancer
formation," Clapper says. "Based on the in vitro data, we think that
NO-naproxen is much better than naproxen in nipping this whole process
in the bud."
To confirm the in vitro results, the team has
treated mice that are genetically predisposed to develop colorectal
adenomas with NO-naproxen and naproxen and are awaiting the results of
this study. NSAIDs have been shown to reduce the risk of colon cancer and
precancerous polyps in people. However, some of the agents have been
taken off the market due to cardiovascular toxicity. With that in mind,
Clapper says, "If we can find something in the same arena that is
effective and nontoxic, it will be extremely valuable."
and other NO-donating NSAID derivatives are a new class of agents being
developed with the aim of reducing gastrointestinal toxicity, a
relatively common side effect associated with NSAIDs.
The first author on the study is EunRan Suh. Co-authors include
Christina Ferrara, Esther Kaunga, Harry S. Cooper, and Wen-Chi L. Chang
of Fox Chase and Ronald A. Lubet of the National Cancer Institute.
Funding for the study came from the National Cancer Institute, NIH.
Chase Cancer Center is one of the leading cancer research and treatment
centers in the United States. Founded in 1904 in Philadelphia as one of
the nation's first cancer hospitals, Fox Chase was also among the first
institutions to be designated a National Cancer Institute Comprehensive
Cancer Center in 1974. Fox Chase researchers have won the highest
awards in their fields, including two Nobel Prizes. Fox Chase
physicians are also routinely recognized in national rankings, and the
Center's nursing program has received the Magnet status for excellence
three consecutive times. Today, Fox Chase conducts a broad array of
nationally competitive basic, translational, and clinical research,
with special programs in cancer prevention, detection, survivorship,
and community outreach. For more information, visit Fox Chase's Web
site at www.fccc.org or call 1-888-FOX CHASE or (1-888-369-2427).
Presentation Title: Nitric oxide-donating naproxen inhibits
-catenin-mediated TCF signaling in colorectal cancer cells more
effectively than naproxen
Presentation Time: Wednesday, Apr 21, 2010, 8:00 AM -11:00 AM