Compound Aids Cancer Chemotherapy, Study Says
30, 2000. 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,
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
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
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.
of North Carolina at Chapel Hill
I-Kappa B, New Gene Switch, May Make Radiation
and Chemotherapy More Effective (March 1999)