The work -- done using advanced
molecular tools with grape-cell cultures and the target enzyme for
new anti-cancer strategies -- helps to identify which flavonoids in
grapes and red wine are most responsible for anti-cancer qualities,
said Mary Ann Lila, a professor in the Department of Natural
Resources and Environmental Sciences.
Flavonoids are a group of organic
compounds that include numerous water-soluble plant pigments
responsible for colors. They are more abundant in red than in white
The Journal of Agricultural and Food
Chemistry has posted the Illinois study online ahead of regular
publication. The study details a dozen newly discovered constituents
in grape-cell culture extracts and how some of them work
synergistically against an enzyme known as human DNA topoisomerase
II. The enzyme is necessary for the spread of cancer and is commonly
used in cancer research to screen plant chemicals.
"The findings add to the argument
for eating whole foods," said Elvira Gonzalez de Mejia, a professor
in the Department of Food Science and Human Nutrition. "It's very
clear that the synergy is critical. When a cell becomes malignant,
that enzyme is expressed 300 times more than in a normal cell. If we
can find a compound or mixture of compounds that can reduce the
activity of that enzyme, the cancerous cells will die."
The synergistic activity involves
specific phytochemicals from the proanthocyanidin and anthocyanin
classes of the varied flavonoid family. They worked more effectively
against the enzyme than do the previously identified flavonoids
quercetin and resveratrol. Alone, the individual components had less
effect on the enzyme.
"We definitely had very potent
activity against the particular antibody system we were using, which
was that of the critical proliferation stage of carcinogenesis,"
Lila said. "In our subsequent studies now under way in animal
models, we are getting direct evidence that these components in
grapes work synergistically in fighting cancer. They have to work
together to obtain the potency that works."
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In a project funded by the U.S.
Department of Agriculture, the researchers are tracking where
specially radiolabeled flavonoids congregate in rats. "We are
finding that these flavonoids are very bioavailable," de Mejia said.
"By eating the fruit, we know that the bioactive component involved
goes into your bloodstream and relocates to other regions. Before
now, we didn't really know that."
Lila, de Mejia and co-author
Jeong-Youn Jo, a doctoral student in Lila's lab, produced the
grape-cell cultures they tested from red-grape plants specifically
bred for their pigmentation and provided by Cornell University
Using vegetative samples of the
plants, rather than the fruit itself, the Illinois team was able to
quickly produce the whole range of grape flavonoids in greater
quantity. The researchers then extracted individual flavonoids
intact. Their analytic work involved the use of reversed-phase
high-performance liquid chromatography and LC-electrospray
ionization/mass spectrometry to profile the most bioactive
Eventually, Lila said, researchers
may be able to determine reasonable dosages for therapeutic
consumption of flavonoid-rich grapes. Supplements containing
specific flavonoids probably won't result in desired benefits, de
Mejia said, because complementary components required for
synergistic activity may be missing.
"Some of the compounds we identified
have not been reported in cell culture and grapes," de Mejia said.
"Some have high inhibitory activity in the promotion and progression
stages of cancer and have a high probability to work against the
The National Institutes of Health
funded the work reported in the Journal of Agricultural and Food
[Jim Barlow, life sciences editor, News Bureau, University of
Illinois at Urbana-Champaign]