In preclinical experiments, the coupling of a plant-derived compound from a traditional Chinese remedy with transferrin selectively kills human leukemia cells while sparing normal white blood cells, according to an article in the January 28th issue of Life Sciences.

Artemisinin, is derived from the wormwood plant and has been used in China since ancient times to treat malaria. Earlier work by American researchers Henry Lai and Narendra Singh indicated that artemisinin alone could selectively kill cancer cells while leaving normal cells unharmed. The coupling of artemisinin with transferrin significantly improves that selectivity.

"By itself, artemisinin is about 100 times more selective in killing cancer cells as opposed to normal cells," Lai said. "In this study, the new artemisinin compound was 34,000 times more potent in killing the cancer cells as opposed to their normal cousins. So the tagging process appears to have greatly increased the potency of artemisinin’s cancer-killing properties."

In the study, researchers exposed human leukemia cells and white blood cells to the compound. While the leukemia cells quickly died, the white blood cells remained essentially unharmed. Researchers decided to couple artemisinin with transferrin after recognizing that the leukemia cells greatly overexpressed the transferrin receptor compared with normal white blood cells. The researchers bound artemisinin to transferrin at the molecular level.

"We call it a Trojan horse because the cancer cell recognizes transferrin as a natural, harmless protein," Lai said. "So the cell picks up the compound without knowing that a bomb - artemisinin - is hidden inside."

Once inside the cell, the artemisinin reacts with the iron, spawning highly reactive free radicals. The free radicals attack other molecules and the cell membrane, breaking it apart and killing the cell.

According to Lai, that process is what initially piqued his interest in artemisinin about 10 years ago. The wormwood extract was used centuries ago in China, but the treatment became lost over time. In the 1970s, it was rediscovered as part of an ancient manuscript containing medical remedies, including a recipe that used a wormwood extract. The medical community soon discovered that the extract, artemisinin, worked well against malaria, and it is currently used for that purpose throughout Asia and Africa.

Artemisinin combats malaria because the malaria parasite collects high iron concentrations as it metabolizes hemoglobin in the blood. As science began to understand how artemisinin functioned, Lai said, he began to wonder if the process had implications for cancer treatment.

"I started thinking that maybe we could use this knowledge to selectively target cancer cells," he said. "So far, the outlook appears good."

The next step in development is likely to be testing in animals and, if that is successful, human trials.