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
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
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
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
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
Wormwood - Non-toxic cure for
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 its very selective, Lai said. Its highly toxic to the cancer
cells, but has
a marginal impact on normal breast cells.
The compound, artemisinin, isnt
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