WASHINGTON, DC—The most active component of green tea, the polyphenol epigallocatechin gallate (EGCG), targets a protein that is expressed two to 10 times higher than normal in many cancer cells, according to a research study presented here at a news briefing at the National Press Club and at an international conference on diet and cancer sponsored by the American Institute for Cancer Research (AICR).
The study was funded by the National Institutes of Health and AICR; the researchers received no money from the tea industry. The University of Rochester study is believed to be the first to show that EGCG binds to the culprit protein hsp90, and may exert its chemoprotective effects—which have been noted in cellular, animal, and human studies—through its interaction with hsp90. The research could lead to anti-cancer drugs containing EGCG.
The study on a molecular mechanism for EGCG's protective effects was one of six on green tea presented at the conference. “The scientists that we have brought together this year are talking about green tea,” said AICR's Vice President for Education and Communications, Jeffrey R. Prince, PhD, who noted that so far in just 2005, more than 100 scientific papers have been published on EGCG's potential anti-cancer benefits.
The hsp90 protein is an aryl hydrocarbon receptor “chaperone” protein, which exists as a master regulator that helps stabilize other proteins (for example, p53 and Erb-b) important in oncogenic processes, said the lead researcher on the green tea study, Thomas A. Gasiewicz, PhD, Professor of Environmental Medicine and Deputy Director of the Environmental Health Sciences Center at the University of Rochester School of Medicine.
“In some circumstances, hsp90 helps to trigger the cascade of events that eventually leads to cancer.” He added that his research has shown that green tea blocks the toxic effects of dioxin, a carcinogenic herbicide, and that EGCG's direct binding to the hsp90 protein—which prevents that protein from sending signals that can start the cancerous process—is most likely the mechanism that protects cells against the toxic effects of dioxin.
In the United States, according to a new AICR survey of 1,008 people, 68% of Americans drink green tea rarely or never. In Japan, in contrast, 65% of people say they drink green tea five or more times a week.
AICR advises people concerned about cancer risk to add two to three cups a day of green tea to a diet rich in a variety of plant foods and low in fat and salt, unless they cannot tolerate caffeine (green tea contains caffeine unless it is specifically sold as decaffeinated green tea).
Since in large doses green tea can interact with blood thinners such as aspirin and warfarin, people taking those drugs should check with their physician before adding green tea to their diet, the organization advises.
On June 30, the Food and Drug Administration released a health advisory—under its Consumer Health for Better Nutrition Initiative—warning that existing evidence does not support qualified health claims for green tea consumption and a reduced risk of breast or prostate cancer, or for any other cancer.
The FDA noted that two studies did not show that drinking green tea reduced the risk of breast cancer, while one weaker and more limited study did show a lower risk; one weak and limited study did not show that drinking green tea reduced the risk of prostate cancer, while another weak and limited study did show a reduced risk.
Based on these studies, the FDA said it is “highly unlikely” that green tea reduces the risk of breast or prostate cancer. The agency stated, however, that it will continue to evaluate new information on foods and dietary supplements, including green tea, and health claims to determine whether changes in either the claims or its decision are necessary.
Asked about the FDA advisory, Dr. Gasiewicz said the problem is that no one really knows what dose of green tea one would need to achieve an anti-cancer effect.
“The animal data are much more intriguing and much more firm” than human data, he said, noting that “the epidemiology is not clear.”
The study is believed to be the first to show that EGCG binds to the culprit protein hsp90, and may exert its chemoprotective effects—which have been noted in cellular, animal, and human studies—through its interaction with hsp90.
In humans, some studies show that green tea is protective against certain cancers, notably prostate and gastrointestinal, while other studies show little or no protection. What is known to date, he said, is that EGCG has “very low toxicity.”
Dr. Gasiewicz said he believes that a more realistic approach than trying to get the protective effects from drinking green tea will eventually be consumption of an anti-cancer agent that contains EGCG.
“If you can't get enough green tea inside you, maybe we can design therapeutic agents” that supply anti-cancer protection, he said. Thus hsp90 inhibitors might become a new approach to chemoprevention, he theorized.
Inhibit Transcriptional Activation
In a second study presented at the AICR meeting, Zigang Dong, MD, DrPH, Professor at the Hormel Institute at the University of Minnesota, presented research from cell culture and mouse models showing that EGCG in green tea and theaflavins, the major active components in black tea, may exert their chemopreventive, anti-cancer effects by inhibiting some transcriptional activation that can lead to cell transformation.
“Signal transduction molecules are really excellent targets for cancer preventive agents,” Dr. Dong said.
Modulate Cellular Signaling Involved in Chronic Inflammation
And a third study highlighted the ability of some phytochemicals, including EGCG, to modulate the cellular signaling involved in chronic inflammation that may be linked to an increased risk of cancer. EGCG is known to interact with NfkB, a key regulator of immune and inflammatory responses.
“Inflammation has long been suspected to contribute to carcinogenesis,” noted Young-Joon Surh, PhD, Professor and Chief of the National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University in Seoul.
“A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer,” he added.
Dr. Surh cited specific transcription factors that play a role in correcting potential destructive cellular functions caused by abnormal proinflammatory signal transmission. “Modulation of cellular signaling involved in the chronic inflammatory response by anti-inflammatory agents provides a rational and pragmatic strategy in molecular, target-based chemoprevention,” he said.
The NIH is currently funding several clinical trials to test the safety and efficacy of green tea in humans. The trials include primary cancer prevention, cancer recurrence and integrative cancer therapy, in which green tea is used in combination with cancer chemotherapy.