OT.....reason to eat red grapes, red wine and peanuts.....Study seems to show why French suffer less heart disease, cancer
CHAPEL HILL - University of North Carolina at Chapel Hill scientists have discovered why a compound found
in grapes and grape products such as red wine shows natural cancer-fighting properties that might be important in
preventing or treating the illness.
The work appears to explain the so-called "French paradox" -- the fact that French people experience lower
rates of heart disease death and certain cancers despite drinking more wine on average than U.S. residents do.
Scientists found that the substance, trans-Resveratrol, or Res, modulates the activity of NF-kappa B, a protein
that attaches to DNA inside cell nuclei and turns genes on and off like a switch, the scientists found. Res
apparently helps turn off a natural protective mechanism in the body involving the protein that prevents cancer cells
from being killed, as they should be.
A report on the work appears in the July issue of Cancer Research, a scientific journal. Authors are Dr. Minnie
Holmes-McNary, a nutritional biologist and postdoctoral fellow at the UNC-CH School of Medicine's Lineberger
Comprehensive Cancer Center, and her mentor Dr. Albert S. Baldwin Jr., a biology professor who also works at
the center.
"A couple of years ago, a group at the University of Illinois found that Res has both anti-inflammatory and
anti-cancer properties," Holmes-McNary said. "The question then became how does it exert its effects, and that's
what we show in our paper."
Working with cultured human and rat cells, the scientists tested whether Res could inhibit both activation of
NF-kappa B and NF-kappa B-dependent gene expression. They found that Res was a powerful inhibitor of the
protein and appeared to work by controlling activity of another closely related protein called I-kappa B, which
regulates NF-kappa activation.
"Using Res, we were able to promote apoptosis, a process that the body uses to kill cancer cells and other cells it
needs to get rid of," Holmes-McNary said. "When Res was absent from the cell culture system, cancer cells
continued to survive, but when Res was there under experimental conditions, we could successfully promote death
of cancer cells by turning off NF-Kappa B."
Studies are now being planned to reproduce the findings in rodents, she said. If the animal experiments go well,
the scientists may extend their work to humans within a few years. Epidemiological studies suggesting a protective
effect of grapes and grape products such as red wine against heart disease and cancer began in the 1970s.
"This is very exciting work because we believe it explains how diet modulates changes at the molecular level,"
Homes-McNary said. "It provides a molecular rationale for the broad chemo-preventive properties of
trans-Resveratrol and by extention, grapes and grape products."
Because the scientists also were able to inhibit a NF-kappa B dependent gene called MCP-1 that is involved in
inflammation and development of atherosclerosis, the research also applies to cardiovascular disease, she added.
Res is found in many fruits and nuts, but is especially abundant in red grapes, mulberries, raspberries and peanuts,
the scientist said. For that reason, she recommends that people consume more of them. Muscadine grapes,
including scuppernongs, are rich sources of the compound.
Three years ago, Baldwin and other UNC-CH researchers first reported that NF-kappa B enables many cultured
tumor cells to escape death when subjected to cancer-killing chemicals. After developing resistance to
chemotherapy, cancer cells they studied continued reproducing and showed no ill effects from the treatment.
Last year, the scientists used a novel cancer gene therapy strategy to block NF-kappa B in mice with I-kappa B.
Human tumors growing in the mice then became susceptible to chemotherapy and in some cases disappeared
altogether following treatment.
Previously, no one had understood why many tumors become unresponsive to chemotherapy and radiation after a
while, Baldwin said. NF-kappa B appears to be a front-line defense protecting both healthy cells -- and
unfortunately cancer cells as well -- from chemical attack and other trauma.
In experiments reported last year, Baldwin and Dr. James C. Cusack Jr. of UNC-CH concentrated on human
colorectal and fibrosarcoma tumors. They grew the tumors in mice and then treated them with a modified form of
the inhibitor I-kappa B carried by a virus that could enter tumor cells. Treatment with a commonly used
chemotherapy compound known as CPT-11 was far more successful, Baldwin said, when coupled with I-kappa
B than when used by itself.
"These potential therapies, combined with dietary interventions such as incorporation of Res into the diet, hold
exciting possibilities for cancer treatment," Holmes-McNary said.
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