[PHNUTR-L] Substance in tree bark could lead to new lung-cancer treatment

[Kathrynne Holden]

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Substance in tree bark could lead to new lung-cancer treatment

Media Contact: Connie Piloto
214-648-3404
connie.piloto at utsouthwestern.edu

DALLAS – June 25, 2007 – Researchers at UT Southwestern Medical Center 
have determined how a substance derived from the bark of the South 
American lapacho tree kills certain kinds of cancer cells, findings that 
also suggest a novel treatment for the most common type of lung cancer.

             The compound, called beta-lapachone, has shown promising 
anti-cancer properties and is currently being used in a clinical trial 
to examine its effectiveness against pancreatic cancer in humans. Until 
now, however, researchers didn’t know the mechanism of how the compound 
killed cancer cells.

             Dr. David Boothman, a professor in the Harold C. Simmons 
Comprehensive Cancer Center and senior author of a study appearing 
online this week in the Proceedings of the National Academy of Sciences, 
has been researching the compound and how it causes cell death in 
cancerous cells for 15 years.

             In the new study, Dr. Boothman and his colleagues in the 
Simmons Cancer Center found that beta-lapachone interacts with an enzyme 
called NQO1, which is present at high levels in non-small cell lung 
cancer and other solid tumors. In tumors, the compound is metabolized by 
NQO1 and produces cell death without damaging noncancerous tissues that 
do not express this enzyme.

             “Basically, we have worked out the mechanism of action of 
beta-lapachone and devised a way of using that drug for individualized 
therapy,” said Dr. Boothman, who is also a professor of pharmacology and 
radiation oncology.

             In healthy cells, NQO1 is either not present or is 
expressed at low levels. In contrast, certain cancer cells – like 
non-small cell lung cancer – overexpress the enzyme. Dr. Boothman and 
his colleagues have determined that when beta-lapachone interacts with 
NQO1, the cell kills itself. Non-small cell lung cancer is the most 
common type of lung cancer.

Beta-lapachone also disrupts the cancer cell’s ability to repair its 
DNA, ultimately leading to the cell’s demise. Applying radiation to 
tumor cells causes DNA damage, which results in a further boost in the 
amount of NQO1 in the cells.

             “When you irradiate a tumor, the levels of NQO1 go up,” Dr. 
Boothman said. “When you then treat these cells with beta-lapachone, you 
get synergy between the enzyme and this agent and you get a whopping kill.”

In the current study, Dr. Boothman tested dosing methods on human tumor 
cells using a synthesized version of beta-lapachone and found that a 
high dose of the compound given for only two to four hours caused all 
the NQO1-containing cancer cells to die.

Understanding how beta-lapachone works to selectively kill 
chemotherapy-resistant tumor cells creates a new paradigm for the care 
of patients with non-small cell lung cancer, the researchers said. They 
are hoping that by using a drug like beta-lapachone, they can 
selectively target cancer tumors and kill them more efficiently. The 
current therapy for non-small cell lung cancer calls for the use of 
platinum-based drugs in combination with radiation.

“Future therapies based on beta-lapachone and NQO1 interaction have the 
potential to play a major role in treating devastating drug-resistant 
cancers such as non-small cell lung cancer,” said Dr. Erik Bey, lead 
author of the study and a postdoctoral researcher in the Simmons Cancer 
Center. “This is the first step in developing chemotherapeutic agents 
that exploit the proteins needed for a number of cellular processes, 
such as DNA repair and programmed cell death.”

             About 85 percent of patients with non-small cell lung 
cancer have cancer cells containing elevated levels of the NQO1 enzyme, 
which is produced by a certain gene. Patients who have a different 
version of the gene would likely not benefit from treatment targeting 
NQO1, Dr. Boothman said.

             Dr. Boothman cautioned that clinical trials of 
beta-lapachone in lung cancer patients will be needed to determine its 
effectiveness as a treatment. He and his team have created a simple 
blood test that would screen patients for the NQO1 enzyme.

Along with Dr. Jinming Gao’s laboratory in the Simmons Cancer Center and 
a joint collaboration with the bioengineering program at UT Dallas, 
researchers in the new “Cell Stress and Cancer Nanomedicine” initiative 
within the Simmons Cancer Center have developed novel nanoparticle drug 
delivery methods for the tumor-targeted delivery of this compound. These 
delivery methods have the promise of further improving this drug for 
non-small cell lung cancer.

Other Simmons Cancer Center researchers involved in the study were Dr. 
Ying Dong, postdoctoral researcher; Dr. Chin-Rang Yang, assistant 
professor; and Dr. Gao, associate professor. UT Southwestern’s Dr. John 
Minna, director of the Nancy B. and Jake L. Hamon Center for Therapeutic 
Oncology Research and the W.A. “Tex” and Deborah Moncrief Jr. Center for 
Cancer Genetics, and Dr. Luc Girard, assistant professor of 
pharmacology, also participated along with researchers from Case Western 
Reserve University and UT M.D. Anderson Cancer Center.

The research was supported by the National Institutes of Health.
###
This news release is available on our World Wide Web home page
at www.utsouthwestern.edu/home/news/index.html
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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