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Researchers Hope Understanding How Some Foods
Prevent Cancer Can Lead to a Preventive Drug
July 9, 2005 Some things we eat and drink, like
broccoli and red wine, have been shown to prevent cancer. Now
researchers are trying to unravel the biochemical mechanism by which
these substances combat cancer.
There goal is that if scientist understand how
these substances stop cancer, then it may be possible to replicate the
action in a cancer-preventing drug.
"Compounds like sulforaphane in broccoli and
resveratrol in wine have been shown to prevent cancer," said Andrew
Mesecar, associate professor of pharmaceutical biotechnology in the
University of Illinois at Chicago College of Pharmacy. "They do that by
signaling our bodies to ramp up the production of proteins capable of
preventing damage to our DNA.
"We now have a good idea how that signal works."
Two key proteins, Keap1 and Nrf2, are involved in
spurring the defense against cancer when disease-preventing foods are
ingested, according to Mesecar and post-doctoral researcher Aimee Eggler.
Keap1, the sensor protein, detects the presence of dietary compounds
like sulforaphane when they link with its cysteine residues, one of the
amino acids that make up proteins. Keap1 binds to Nrf2, the messenger
that turns on the genes for the protective proteins, averting DNA
damage.
"Earlier studies in mice suggested that natural
cancer-preventing compounds worked by severing the tie between Keap1 and
Nrf2, freeing Nrf2 to take action," Mesecar said. "But the signaling
doesn't happen this way in humans."
The scientists found that in humans the connection
between the two proteins is not broken.
What's important, the researchers said, is the
modification of cysteines in Keap1. They found that one particular
cysteine was among the most likely to be altered in the interaction with
cancer-preventing compounds.
That finding corresponded with results from other
researchers. As a result, the scientists are proposing that the
alteration of just this one amino acid in Keap1 is the critical step
that spurs higher levels of the messenger Nrf2 and, consequently,
increased production of the protective proteins.
Keap1 is a promising new target for drugs to fight
many different kinds of cancer, Mesecar said.
The American Cancer Society estimates that there
will be over 1.3 million new cases of cancer in 2005, and roughly half
of these individuals will not survive their disease, Mesecar noted.
Senior citizens are the most susceptible to developing cancer.
"One way of preventing cancer may be to eat certain
foods rich in cancer-preventing compounds. An alternative is identifying
how these compounds work and replicating their modes of action with
drugs," he said.
Mesecar's and Eggler's main collaborators in the
study were Richard van Breemen, professor of medicinal chemistry and
pharmacognosy in the UIC College of Pharmacy, and Guowen Liu, a graduate
student at UIC. John Pezzuto, professor of medicinal chemistry and
molecular pharmacology at Purdue University, is also an author of the
study.
About the study:
The findings are published in this week's Early
Edition of the Proceedings of the National Academy of Sciences. The
research was funded by the National Cancer Institute.
For more information about the UIC College of
Pharmacy, visit
www.uic.edu/pharmacy/.
UIC ranks among the nation's top 50 universities in
federal research funding and is Chicago's largest university with 25,000
students, 12,000 faculty and staff, 15 colleges and the state's major
public medical center. A hallmark of the campus is the Great Cities
Commitment, through which UIC faculty, students and staff engage with
community, corporate, foundation and government partners in hundreds of
programs to improve the quality of life in metropolitan areas around the
world.
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