Grape Compound Aids Cancer
Chemotherapy, Study Says
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, according to
scientists at University of North Carolina at Chapel Hill.
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 trans-Resveratrol, or Res, apparently
helps turn off a protein in the body that prevents cancer cells
from being killed, as they should. The protein, called NF-kappa B,
attaches to DNA inside cell nuclei and turns genes on and off like
a switch.
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 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.
Muscadine wines contain up to seven times more resveratrol than
regular wines
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.
Support for the studies came from the National Cancer Institute
and the N.C. affiliate of the American Heart Association.
Source: U of North Carolina. Story posted June 30, 2000.
Page links last updated Dec 21 2003.
Links
University of North
Carolina at Chapel Hill
I-Kappa
B, New Gene Switch, May Make Radiation and Chemotherapy More
Effective (March 1999)
