|New Compound May Protect Against Liver Cancer
Researchers have identified a new compound called CDDO-Im that protects against
the development of liver cancer in laboratory animals. The compound appears to
stimulate the enzymes that remove toxic substances from the cells, thereby increasing
the cells’ resistance to cancer-causing toxins. The National Institute of Environmental
Health Sciences and the National Cancer Institute, agencies of the federal National
Institutes of Health, provided funding to researchers at the Johns Hopkins Bloomberg
School of Public Health for the two-year study.
The compound’s effectiveness at very low doses suggests it may have similar
cancer-fighting properties in humans. Researchers believe it may be particularly
effective in preventing cancers with a strong inflammatory component, such as
liver, colon, prostate and gastric cancers. The compound could eventually play
a preventive role in a wide range of other illnesses such as neurodegenerative
disease, asthma and emphysema.
The study results are featured on the cover of the February 15, 2006 issue of
the journal Cancer Research.
“The results show that the potency of this compound is more than 100 times as
great as that of other chemopreventive agents in protecting against cancer,” said
NIEHS Director David A. Schwartz, M.D. “This protective effect, combined with
the compound’s anti-inflammatory properties, make it an exciting avenue for the
prevention of other diseases as well.”
CDDO-Im belongs to a class of cancer-fighting compounds called triterpenoids.
It is a synthetic compound derived from oleanolic acid, a naturally occurring
substance found in plants all over the world. Research with other oleanolic derivatives
showed marked anti-tumor activity in both animals and humans.
To test the effectiveness of CDDO-Im, researchers treated laboratory rats with
either 0.1, 0.3, 1.0, 3.0 or 10 micromole doses of the compound. Two days after
treatment with CDDO-Im, the rats were treated with aflatoxin, a naturally occurring
toxin that causes liver cancer in animals.
Evaluation of the rat livers showed that the lowest concentration of CDDO-Im
led to an 85 percent reduction in pre-cancerous lesions, abnormal growths that
have a greater likelihood of developing into actual cancers. “This compound has
a much greater effect at a far lower dose than any other compound currently used
for preventing aflatoxin-induced cancer in humans,” said Thomas Kensler, Ph.D.,
a cancer biologist with the Johns Hopkins Bloomberg School of Public Health and
lead author on the study.
According to Kensler, CDDO-Im activates a protein called Nrf2 that plays a central
role in protecting the cells against the toxic effects of environmental agents. “Nrf2
directs certain genes to stimulate the cell’s defense mechanisms,” he said. “The
protein also stimulates key enzymes that can detoxify harmful agents like aflatoxin
and remove them from the cell.”
Like other compounds derived from oleanolic acid, CDDO-Im also has strong anti-inflammatory
properties that make it ideally suited to the prevention of certain cancers. “When
cells become inflamed, they can produce reactive molecules called free radicals
that can damage DNA and promote cancer development,” said Kensler. “CDDO-Im can
also inhibit cancer formation by interfering with this inflammatory process.”
Because it can stimulate the body’s cancer-fighting capabilities at such low
doses, Kensler believes that CDDO-Im is an excellent candidate for cancer prevention
use in humans. “If this compound can produce such a potent and dramatic reduction
in the number of pre-cancerous growths, it should have an equally dramatic impact
on the development of actual cancers,” he said.
In addition to serving as a valuable tool in the development of new cancer prevention
interventions, CDDO-Im may offer protection in a wide range of other disease
settings. “We know that the Nrf2 protein plays a role in regulating many different
kinds of genes involved in protecting the cell from harmful agents,” said Kensler. “It
follows that activation of the Nrf2 pathway with CDDO-Im could provide protection
against a number of diseases where environmental agents play important roles
in their causes.”
Note: Triterpenoid compounds are currently under development by Dr. Michael
Sporn and colleagues at Dartmouth Medical School.
NIEHS, a component of the National Institutes of Health, supports research to
understand the effects of the environment on human health. For more information
on cancer prevention and other environmental health topics, please visit the
NIEHS website at http://www.niehs.nih.gov/home.htm.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.