A recent study has found that a substance derived from the bark of the South American lapacho tree kills certain kinds of cancer cells.
The study, conducted at UT Southwestern Medical Center, has also suggested that this substance could lead to a novel treatment for the most common type of lung cancer.
The compound, called beta-lapachone, has shown promising anti-cancer properties and is presently being used in a clinical trial to inspect its efficiency 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 networks 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, over express the enzyme. Dr. Boothman and his colleagues have found out that when beta-lapachone interacts with NQO1, the cell kills itself.
Beta-lapachone also upsets the cancer cell's ability to refurbish its DNA, eventually leading to the cell's termination.
"When you irradiate a tumor, the levels of NQO1 go up. When you then treat these cells with beta-lapachone, you get synergy between the enzyme and this agent and you get a whopping kill," Dr. Boothman said.
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.
Researchers said that by using a drug like beta-lapachone, they are hoping to selectively target cancer tumors and kill them more powerfully.
"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 gain from treatment targeting NQO1, Dr. Boothman said.
Dr. Boothman cautioned that clinical trials of beta-lapachone in lung cancer patients will be needed to establish its effectiveness as a treatment. He and his team have created a simple blood test that would screen patients for the NQO1 enzyme.