Danforth researcher: Compounds found in green tea show promise in treating tumors
The cases were initially baffling. Children were turning up with too much insulin in their blood as well as an excess of ammonia, sometimes building to toxic levels. Merely consuming too much protein could induce hypoglycemic coma or even death.
"This was a very unique set of symptoms," said Thomas Smith of the Donald Danforth Plant Science Center. "You might have a tumor in your pancreas and you secrete too much insulin. That's hyper insulinism. But you never get this ammonia link."
However, the rare genetic disorder that brought about that unusual combination of symptoms has now become part of a complex web of research that may eventually lead to more effective treatments of cancerous tumors based on compounds found in green tea.
Smith, who has been studying those compounds since he wrote his doctoral thesis, is principal investigator of research recently published in the Journal of Biological Chemistry. It outlines the mechanics of green tea compounds called polyphenols and their interaction with glutamate dehydrogenase (GDH), an enzyme that breaks down amino acids in cells.
Though found in all living things, GDH acts as a largely crude and uncontrolled instrument in plants and bacteria. Yet in animals it works very differently, responding to a number of metabolites that regulate its action very precisely. Smith compares it to the enzyme having an accelerator and a brake.
"We've known about this for years, but we've never known why," Smith said. "It never made any sense. I think that we are much more sophisticated and we need really fine, sensitive control turning this enzyme up and down. We want a very fast response, a very fine-tuned response."
Unfortunately, it was a response lacking in the group of patients who were developing too much insulin and ammonia.
"They had a genetic mutation that got rid of the brake," Smith said. "They couldn't shut the enzyme off. It just ran amok."
However, research suggested that the green tea polyphenols could short-circuit that process, providing eventual hope for treatment to help those with the often-fatal illness.
The story may have even larger implications. Cancer researchers picked up on the work, believing that disabling GDH could have an effect on certain cancers.
"Essentially, tumors are addicted to needing lots of energy because they are growing so fast," Smith said. "They'll get the energy either from sugar or amino acids. If you are going to be using amino acids for food, you are going to be going through my enzyme."
What they found was the tumors began to die, essentially starved to death by the newly inactive GDH.
The paper released this month, co-authored with researchers at the Children's Hospital of Philadelphia and the University of Pennsylvania, furthers understanding of how the proteins involved bind at the atomic level through research on mice.
In the meantime, tumor research has continued elsewhere. The green tea compounds have even been found to penetrate the brain, an important quality in the treatment of aggressive tumors called glioblastomas. The other type of tumor under study is a nonmalignant variety caused by tuberous sclerosis complex disorder.
However, Smith said that as promising as the ongoing work may be, there's still a long way to travel.
"The problem is that these compounds are unstable, poorly absorbed and may have multiple effects on several different systems," Smith said. "To do any kind of clinical application, you really have to have it narrowed down to what's the cause and effect."
That makes the polyphenols largely ineffective as drugs. However, Smith said the compounds might form the basis for future treatments nonetheless.
Meanwhile, the effects of simply drinking green tea remain debatable. In fact, Smith cautions that recent research suggests that under certain circumstances consuming the tea may be counterproductive, hindering anti-cancer agents for those undergoing chemotherapy.
"There are a million clinical trials underway," he said of studies on tea drinking. "I think the jury is still out on it."
Still, he thinks the future looks a little brighter with the opening of a new potential avenue for treatment.
"At the end of the day, half the battle of drug design is finding something that works, then you try and make it better," he said. "That's what we've got now. We've got something that works really well."
David Baugher is a freelance writer in St. Louis. To reach him, contact Beacon health and science editor Sally J. Altman.
