http://www.newswise.com/articles/view/509720/

Source: University of Washington     Released: Tue 08-Feb-2005, 16:10
ET

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Researchers Blend Folk Treatment, High Tech for Promising Anti-cancer
Compound
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Medical News   Keywords
CANCER, FOLK MEDICINE, BIOCHEMISTRY, ARTEMISININ, WORMWOOD
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Researchers at the University of Washington have blended the past with
the present in the fight against cancer, synthesizing a promising new
compound from an ancient Chinese remedy to selectively target cancer
cells.

Newswise - Researchers at the University of Washington have blended
the past with the present in the fight against cancer, synthesizing a
promising new compound from an ancient Chinese remedy that uses cancer
cells' rapacious appetite for iron to make them a target.

The substance, artemisinin, is derived from the wormwood plant and has
been used in China since ancient times to treat malaria. Earlier work
by Henry Lai and Narendra Singh, both UW bioengineers, indicated that
artemisinin alone could selectively kill cancer cells while leaving
normal cells unharmed.

The new compound appears to vastly improve that deadly selectivity,
according to a new study that appeared in a recent issue of the journal
Life Sciences. In addition to Lai and Singh, co-authors include
Tomikazu Sasaki and Archna Messay, both UW chemists.

"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."

The compound has been licensed to Chongqing Holley Holdings and Holley
Pharmaceuticals, its U.S. subsidiary, to be developed for possible use
in humans. Although the compound is promising, officials say, potential
use for people is still years away.

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.

The trick to the compound's effectiveness, according to Lai, appears to
be in taking advantage of how cancer cells function.

Because they multiply so rapidly, most cancer cells need more iron than
normal cells to replicate DNA. To facilitate that, cancer cells have
inlets on their surface, known as transferrin receptors, in greater
numbers than other cells. Those receptors allow quick transport into
the cell of transferrin, an iron-carrying protein found in blood.

In creating the compound, researchers bound artemisinin to transferrin
at the molecular level. The combination of the two ingredients appears
to fool the cancer cell.

"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 chemicals called "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 under the Holley licensing agreement will
likely be testing in animals and, if that pans out, human trials to
gauge the compound's effectiveness. The current study was funded by the
Artemisinin Research Foundation and Chongqing Holley Holdings.

The article is available on-line at
http://www.sciencedirect.com/science. Click the "journals" button and
look under Life Sciences, Volume 76, Issue 11. The article is No. 9 on
the Web page (page 1267-1279).

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