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

aduate 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 recepto
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Source:University of Rochester Medical Center


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