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Wormwood


Ancient Chinese remedy shows potential in preventing breast cancer

A derivative of the sweet wormwood plant used since ancient times to fight malaria and shown to precisely target and kill cancer cells may someday aid in stopping breast cancer before it gets a toehold. In a new study, two University of Washington bioengineers found that the substance, artemisinin, appeared to prevent the onset of breast cancer in rats that had been given a cancer-causing agent. The study appears in the latest issue of the journal Cancer Letters.

"Based on earlier studies, artemisinin is selectively toxic to cancer cells and is effective orally," according to Henry Lai, research professor in the Department of Bioengineering, who conducted the study with fellow UW bioengineer Narendra P. Singh, a research associate professor in the department. "With the results of this study, it's an attractive candidate for cancer prevention."

The properties that make artemisinin an effective antimalarial agent also appear responsible for its anti-cancer clout. When artemisinin comes into contact with iron, a chemical reaction ensues that spawns free radicals -- highly reactive chemicals that, when formed inside a cell, attack the cell membrane and other structures, killing the cell.

The malaria parasite can't eliminate iron in the blood cells it eats, and stores it. Artemisinin makes that stored iron toxic to the parasite.

The same appears to be true for cancer. Because they multiply so rapidly, most cancer cells have a high rate of iron uptake. Their surfaces have large numbers of receptors, which transport iron into the cells. That appears to allow the artemisinin to selectively target and kill the cancer cells, based on their higher iron content.

In the latest study, the researchers administered to rats a single oral dose of 7,12-dimethylbenz[a]anthracene, a substance known to induce multiple breast tumors. Half of the rats then were fed regular food, while the other half were fed food with 0.02 percent artemisinin added. For 40 weeks, researchers monitored each group for the formation of breast tumors.

Among the rats that didn't get artemisinin, 96 percent developed tumors. In comparison, 57 percent of the artemisinin-fed rats developed tumors.

In addition, the researchers report, tumors that did develop in the artemisinin-fed rats were both "significantly fewer and smaller in size when compared with controls."

The reason for artemisinin's apparent preventative effect may be twofold, the researchers said. The substance may kill precancerous cells, which also tend to use more iron than ordinary cells, before those cells develop into a tumor. Artemisinin also may impede angiogenesis, or a tumor's ability to grow networks of blood vessels that allow it to enlarge.

Because artemisinin is widely used in Asia and Africa as an anti-malarial, it has a track record of being relatively safe and causing no known side effects, Lai said. "The present data indicate that it may be a potent cancer-chemoprevention agent.

"Additional studies are needed to investigate whether the breast cancer prevention property of artemisinin can be generalized to other types of cancer."

Chongqing Holley Holdings, a Chinese company, and Holley Pharmaceuticals, its U.S. subsidiary, supported the research. The company, located in Chongqing, China, has been in the artemisinin business for more than 30 years and is a world leader in farming, extracting and manufacturing artemisinin, its derivatives and artemisinin-based anti-malaria drugs.


Researchers blend folk treatment, high tech for promising anti-cancer compound

University of Washington

Death of a killer: A human leukemia cell, center, is destroyed by artemisinin-tagged holotransferrin, a new compound engineered at the University of Washington to sneak past a cancer cell's membrane, then release an artemisinin "bomb" once inside.

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.

CONTACT: Rob Harrill rharrill@u.washington.edu 206-543-2580 


Wormwood - Non-toxic cure for cancer
Two bioengineering researchers at the University of Washington have discovered a promising potential treatment for cancer among the ancient arts of Chinese folk medicine. Research Professor Henry Lai and assistant
research Professor Narendra Singh have exploited the chemical properties of a wormwood derivative to target breast cancer cells, with surprisingly effective results.

A study in the latest issue of the journal Life Sciences describes how the derivative killed virtually all human breast cancer cells exposed to it within 16 hours. “Not only does it appear to be effective, but it’s very selective,” Lai said. “It’s highly toxic to the cancer cells, but has
a marginal impact on normal breast cells.”

The compound, artemisinin, isn’t new. It apparently was extracted from the plant Artemisia annua L., commonly known as wormwood, thousands of years ago by the Chinese, who used it to combat malaria. However,
the treatment was lost over time. Artemisinin was rediscovered during an archaeological dig in the 1970s that unearthed recipes for ancient medical
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