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Darrell E. Ward, Ohio State University
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New research strongly suggests that a mix of preventative agents,
such as those found in concentrated black raspberries, may more
effectively inhibit cancer development than single agents aimed at
shutting down a particular gene. Researchers at the Ohio State
University Comprehensive Cancer Center examined the effect of
freeze-dried black raspberries on genes altered by a chemical
carcinogen in an animal model of esophageal cancer.
The carcinogen affected the activity of some 2,200 genes in the
animals' esophagus in only one week, but 460 of those genes were
restored to normal activity in animals that consumed freeze-dried black
raspberry powder as part of their diet during the exposure.
These findings, published in recent issue of the journal Cancer Research,
also helped identify 53 genes that may play a fundamental role in early
cancer development and may therefore be important targets for
chemoprevention agents.
"We have clearly shown that berries, which contain a variety of
anticancer compounds, have a genome-wide effect on the expression of
genes involved in cancer development," says principal investigator Gary
D. Stoner, a professor of pathology, human nutrition and medicine who
studies dietary agents for the prevention of esophageal cancer.
"This suggests to us that a mixture of preventative agents, which
berries provide, may more effectively prevent cancer than a single
agent that targets only one or a few genes."
Stoner notes that black raspberries have vitamins, minerals, phenols
and phytosterols, many of which individually are known to prevent
cancer in animals.
"Freeze drying the berries concentrates these elements about ten
times, giving us a power pack of chemoprevention agents that can
influence the different signaling pathways that are deregulated in
cancer," he says.
To conduct this study, Stoner and his colleagues fed rats either a
normal diet or a diet containing 5 percent black-raspberry powder.
During the third week, half the animals in each diet group were
injected three times with a chemical carcinogen,
N-nitrosomethylbenzylamine. The animals continued consuming the diets
during the week of carcinogen treatment.
After the third week, the researchers examined the animals'
esophageal tissue, thereby capturing gene changes that occur early
during carcinogen exposure. Their analyses included measuring the
activity, or expression levels, of 41,000 genes. In the
carcinogen-treated animals, 2,261 of these genes showed changes in
activity of 50 percent or higher.
"These changes in gene expression correlated with changes in the
tissue that included greater cell proliferation, marked inflammation,
and increased apoptosis," Stoner says.
In the animals fed berry powder, however, a fifth of the carcinogen
affected genes – exactly 462 of them – showed near-normal levels of
activity, when compared with controls. Most of these genes are
associated with cell proliferation and death, cell attachment and
movement, the growth of new blood vessels and other processes that
contribute to cancer development. The tissue also appeared more normal
and healthy.
Lastly, of the 462 genes restored to normal by the berries, 53 of
them were also returned to normal by a second chemoprevention agent
tested during a companion study.
"Because both berries and the second agent maintain near-normal
levels of expression of these 53 genes, we believe their early
deregulation may be especially important in the development of
esophageal cancer," Stoner says.
"What's emerging from studies in cancer chemoprevention is that
using single compounds alone is not enough," Stoner says. "And berries
are not enough. We never get 100 percent tumor inhibition with berries.
So we need to think about another food that we can add to them that
will boost the chemopreventive activities of berries alone."
Source: Ohio State University
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