*Article: Green Tea’s Cancer-fighting Allure Becomes More Potent

Green tea's ability to fight cancer is even more potent and varied than scientists suspected, say researchers who have discovered that chemicals in green tea shut down one of the key molecules that tobacco relies upon to cause cancer. It's a find that could help explain why people who drink green tea are less likely to develop cancer. The finding by scientists at the University of Rochester's Environmental Health Science Center appears in the July 21 issue of Chemical Research in Toxicology, published by the American Chemical Society.

Graduate student Christine Palermo and adviser Thomas Gasiewicz, Ph.D., set out to measure the effects of the chemicals found in green tea on a molecule known as the aryl hydrocarbon (AH) receptor, a molecule that frequently plays a role in turning on genes that are oftentimes harmful. Gasiewicz has previously shown how both tobacco smoke and dioxin manipulate the molecule – a favorite target of toxic substances – to cause havoc within the body.

The team isolated the chemicals that make up green tea and found two that inhibit AH activity. The two substances, epigallocatechingallate (EGCG) and epigallocatechin (EGC), are close molecular cousins to other flavonoids found in broccoli, cabbage, grapes and red wine that are known to help prevent cancer.

While green tea has been much-ballyhooed for its anti-cancer effects as well as other purported abilities such as preventing rheumatoid arthritis and lowering cholesterol, just how the substance works has been a mystery. Scientists do know that green tea contains chemicals that are anti-oxidants and quench harmful molecules. But its effects on the AH receptor have not been thoroughly evaluated until now.

"It's likely that the compounds in green tea act through many different pathways," says Gasiewicz, professor and chair of Environmental Medicine and director of Rochester's Environmental Health Science Center. "Green tea may work differently than we thought to exert its anti-cancer activity."

Gasiewicz and Palermo showed that the chemicals shut down the AH receptor in cancerous mouse cells, and early results indicate the same is true in human cells as well.

In the laboratory the AH-inhibiting effects of green tea become evident when EGCG and EGC reach levels typical of those found in a cup of green tea. But the scientists say that how green tea is metabolized by the body is crucial to its effectiveness, and that results in the laboratory don't necessarily translate directly to the dinner table.

"Right now we don't know if drinking the amount of green tea that a person normally drinks would make a difference, but the work is giving us insight into how the proteins work," says Palermo, who enjoys cold green tea herself. "There are a lot of differences between various kinds of green tea, so a lot more research is needed."

For this work Palermo received the award for best poster in the chemical carcinogenesis specialty section at the meeting of the Society of Toxicology in March. Now she is studying exactly how green tea inhibits the AH receptor. After she graduates Palermo plans to study links between environmental agents and childhood leukemia.


In addition to Palermo and Gasiewicz, other authors are former post-doctoral associate Jose Martin Hernando and chemist Andrew Kende, who teased apart the components of green tea extract; and Stephen Dertinger, a former student who first had the idea to test green tea's effects on the AH receptor. The work was funded by the National Institute of Environmental Health Sciences and the American Institute for Cancer Research.

Source: University Of Rochester Medical Center
Date: 2003-08-05
URL: http://www.sciencedaily.com/releases/2003/08/030805072109.htm

More:


While on trail of dioxin, scientists pinpoint cancer target of green tea
16 May 2005

Green tea appears to protect against cancer by affecting a "promiscuous" protein that pharmaceutical experts are already targeting in an effort to develop a new drug to stop the disease, scientists at the University of Rochester Medical Center have found. The research, which buttresses beliefs about the health benefits of green tea with solid scientific evidence, has been cited as part of the best doctoral thesis produced by a student at the university's School of Medicine and Dentistry this year.

The thesis by student Christine Palermo is part of a wider research project led by toxicologist Thomas A. Gasiewicz, Ph.D., whose decades-long studies of the harmful effects of dioxin ultimately led his group to explore the protective effects of green tea. While it's been reported that green tea protects people against some forms of cancer, such as breast and liver cancer, exactly how it does so has been difficult to pinpoint.

The latest results make more feasible the idea of harnessing green tea's protective power. Just as people with aches and pains no longer have to chew on willow bark to receive the benefits of the substance salicin - they simply take an aspirin -the current research opens the door to extending the health benefits first discovered in green tea to people who never touch the beverage. Isolating the chemicals that protect against cancer would also sidestep questions such as how to take into account different types of teas and different brewing processes, or how much tea one needs to drink.

"It's important to find out the source of green tea's protective effects," says Gasiewicz, professor and chair of Environmental Medicine and director of Rochester's Environmental Health Science Center. "What is exciting here is that a completely new mechanism has been found that very well could be responsible for its protective effects, and that could help us find a compound that is much more potent."

Palermo, Gasiewicz, and current undergraduate Claire Westlake discovered that a chaperone protein known as HSP90 is involved in conferring green tea's protective effects. Other researchers have shown that many cancer cells have an increase in the level of HSP90 compared to healthy cells, and that when HSP90 is blocked, levels of proteins that make cancer cells grow drop.

Drug makers are currently working on ways to block HSP90, which is known as a promiscuous chaperone protein because it binds to many different cells and receptors in the body. It turns out that those researchers are trying to duplicate what green tea does naturally. Gasiewicz says drug makers can learn from green tea, which might modulate HSP-90 in a way that researchers haven't seen before.

Gasiewicz is a world leader on dioxin, and it was by tracking the trail of dioxin's harmful effects on the body that his group made the green tea findings. His group has shown how dioxin and other substances like cigarette smoke manipulate a major cancer-causing molecule, the aryl hydrocarbon (AH) receptor, which frequently plays a role in turning on genes that are oftentimes harmful.

Two years ago the team discovered that AH activity is inhibited by a chemical found in white and green teas, epigallocatechingallate or EGCG, a cousin of flavonoids found in broccoli, cabbage, grapes and red wine that are known to help prevent cancer. The team had been working on other chemicals to try to stop AH activity.

"We initially hypothesized that EGCG would work in the same way as other AH antagonists, by binding directly to it. We were completely surprised that this isn't the case," says Gasiewicz, whose work was funded by the National Institute of Environmental Health Sciences and the American Institute for Cancer Research.

Instead, the team found that EGCG binds to HSP90, a protein that helps other proteins stay stable, serving the same role as a tail on a kite. When the two bind, HSP90 no longer turns on the AH receptor, stopping the cascade of events that would lead to the activation of several harmful genes.

This weekend Palermo is receiving the Wallace Fenn Award, named after a long-time physiology professor at the University of Rochester School of Medicine and Dentistry. The award is given at graduation each year to a student who has produced an outstanding thesis. The research also has earned Palermo awards from the Society of Toxicology in each of the last three years; the current research was published in the April 5 issue of the journal Biochemistry. She is now a post-doctoral associate at Tulane, where she is looking into the causes of childhood leukemia.

Source: http://www.medicalnewstoday.com/medicalnews.php?newsid=24496#


Contact: Tom Rickey
tom_rickey<at>urmc.rochester<dot>edu
585-275-7954
University of Rochester Medical Center
http://www.urmc.rochester.edu
.