by John C. Martin
Article Date: 02-24-06



A derivative of a ubiquitous substance found in plants may be the
key to protecting people from liver cancer, suggests new research by
doctors at Johns Hopkins University.1

The compound is known by its chemical name: CDDO-Im. Scientists say
it protects lab animals from liver cancer and could be just as
powerful for humans. Studies involving people have yet to be
performed.

"The results show that the potency of this compound is more than 100
times as great" as other cancer-preventing therapies, explained
David Schwartz, MD, director of the National Institute of
Environmental Health Sciences at the NIH, which, along with the
National Cancer Institute, funded the study. "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 works by apparently removing toxic substances from liver
cells, thus increasing the cells' resistance to cancer-causing
poisons. Because it's effective at low doses, the Johns Hopkins
scientists stress that it could have potential for people,
particularly for those who have cancer with an inflammatory
component, such as those of the liver, colon, prostate and stomach.

The compound belongs to a class of cancer-fighting substances known
as triterpenoids (try-ter-puh-NOYDZ); it's manmade and derived from
oleanoic acid (oh-lee-uh-NOE-ik), a naturally-occurring substance
found in plants around the world.

It's also been suggested that other oleanolic-based compounds have
anti-cancer properties.2,3

To determine whether this particular triterpenoid fights off liver
cancer, researchers treated lab rates with varying doses of CDDO-Im.
Two days later, each animal was treated with aflatoxin, a naturally-
occurring toxin that causes liver cancer in animals.

They then evaluated the liver of each rat. Even at the lowest dose,
the compound led to an 85 percent reduction in pre-cancerous lesions
on the organs. These lesions aren't malignant, but have the
potential of eventually developing into cancer. "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 the study's lead investigator, Thomas Kensler, PhD, a cancer
biologist at the Johns Hopkins Bloomberg School of Public Health.

Kensler says CDDO-Im works by activating a protein that plays a key
role in protecting liver cells from the toxic effects of certain
environmental agents. The protein directs specific genes in the body
to "stimulate the cell's defense mechanisms," he explained. "The
protein also stimulates key enzymes that can detoxify agents like
aflatoxin and remove them from the cell."

Since the compound showed its powerful effectiveness on precancerous
lesions in the rodents used in this study, it will likely make an
excellent candidate as a drug to prevent liver cancer itself,
Kensler maintained.

"If this compound can produce such a potent and dramatic reduction
in the number of precancerous growths, it should have an equally
dramatic impact on the development of actual cancers," he said.

1. Yates MS, Kwak MK, Egner PA et al. Potent protection against
aflatoxin-induced tumorigenesis through induction of Nrf2-regulated
pathways by the Triterpenoid 1-[2-Cyano-3,12-Dioxooleana-1,9(11)-
Dien-28-Oyl] Imidazole. Cancer Res 2006 Feb 15;66(4):2488-94.
2. Konopleva M, Tsao T, Estrov Z et al. The synthetic triterpenoid 2-
cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces caspase-
dependent and –independent apoptosis in acute myelogenous leukemia.
Cancer Res 2004 Nov 1;64(21):7927-35.
3. Kim KB, Lotan R, Yue P et al. Identification of a novel synthetic
triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate that
potently induces caspase-mediated apoptosis in human lung cancer
cells. Mol Cancer Ther 2002;1:177-84.

John Martin is a long-time health journalist and an editor for
CuraScript. His credits include overseeing health news coverage for
the website of Fox Television's The Health Network, and articles for
the New York Post and other consumer and trade publications