In what may be a parallel to the work that produced taxanes, researchers have found that a novel compound derived from the bark of a South American tree shows promise against several cancers including non-small cell lung cancer, according to an article in the July 10 issue of the Proceedings of the National Academy of Sciences.

The tree in question is the South American lapacho tree, and the compound is called beta-lapachone. It has shown promising anti-cancer properties and is currently being used in a clinical trial to examine effectiveness against pancreatic cancer. Until now, however, researchers did not 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 the study has been researching the compound and how it causes cell death in cancerous cells for 15 years.

In the current study, Boothman and colleagues 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 the enzyme, producing cell death without damaging noncancerous tissues, which 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 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. The investigators 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,” 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. Patients who have a different version of the gene would likely not benefit from treatment targeting NQO1, Dr. Boothman said.