Mechanism for green tea's anti-cancer action revealed

- Last updated on GMT

Related tags: Green tea, Cancer

Green tea appears to protect against cancer by affecting a
'promiscuous' protein that pharmaceutical experts are already
targeting in their work on anti-cancer drugs, according to new
research.

The study, by PhD student Christine Palermo at the University of Rochester Medical Center, reveals a potential new mechanism to explain the tea, and particularly its active compounds' action against cancer.

While many studies suggest 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.

"It's important to find out the source of green tea's protective effects,"​ said toxicologist Thomas A Gasiewicz, whose work on the harmful effects of dioxin led the Rochester group to explore the protective effects of green tea.

"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 green tea might modulate HSP-90 in a way that researchers have not seen before.

Gasiewicz and his group have 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, now being produced and marketed as a supplement by DSM.

"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,"​ said 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.

Another potential mechanism for green tea's action was outlined recently by a team at the University of Wisconsin and Case Western Reserve University in Cleveland, Ohio. The found that green tea polyphenols reduce levels of insulin-like growth factor-1 (IGF-1) in prostate tumour cells in a mouse model for human prostate cancer. Increased levels of IGF-1 are associated with higher risk of several cancers, such as prostate, breast, lung and colon.

Meanwhile, researchers at Kyushu University in Japan reported last year that EGCG appears to inhibit tumour cell growth by binding to a receptor on cells called the 67-kDa laminin receptor. A variety of tumours produce abnormally high levels of 67 LR, and the receptor is thought to be involved in the spread of cancers through the body.

The new research was published in the 5 April issue of Biochemistry​.

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