While On Trail Of Dioxin, Scientists Pinpoint Cancer Target Of Green Tea

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.