From mgs@aae.wisc.edu Fri Apr  9 01:21:19 1999
Date: Thu, 8 Apr 1999 15:58:04 -0500
From: "Michele Gale-Sinex/CIAS, UW-Madison" 
To: sanet-mg@amani.ces.ncsu.edu
Subject: Fruit/vegie/grain compounds slow tumor cell growth

Howdy, all--

Thought this might interest some of you.

peace
misha

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Science Report

Agricultural and Consumer Press Service	
College of Agricultural and Life Sciences 
440 Henry Mall				
Research Division Madison  WI 53706	
(608) 262-1461		
University of  Wisconsin-Madison

     For Immediate Release
     For More Information:
     Charles Elson (608) 262-1332
     elson@nutrisci.wisc.edu

COMPOUNDS FROM FRUITS, VEGETABLES AND GRAINS
SLOW THE GROWTH OF HUMAN TUMOR CELLS

Evidence points to mechanism of how isoprenoids
inhibit the multiplication of tumor cells and shunt cells to a natural
death

Researchers at the University of Wisconsin-Madison report in current
issue of the Journal of Nutrition that small concentrations of two
compounds from plants we eat suppress the growth of three kinds of
human cancer cells in the laboratory.

"Our studies showed that cancer cells were more sensitive to these
compounds than normal cells and that the two compounds had a
stronger effect when combined than we would have expected from the
action of either alone," says Charles Elson, a nutritional scientist
in the College of Agricultural and Life Sciences.  "Our findings
strengthen the idea that a diet rich in plants is beneficial because
of the large array of plant compounds rather than the singular action
of one kind of plant or one compound in plants."

Elson suggests that the anticarcinogenic activity of these and
similar plant compounds differs from the mechanism of other agents
that block or suppress cancer cell growth.  Unless controlled,
cancer cells typically live and divide indefinitely.

"The two compounds we studied suppress an enzyme," Elson says.  "We
think that this deprives tumor cells of chemical intermediates they
need to multiply.  The two compounds even work on human tumor cell
lines that have mutations known to promote cancer."

Studies consistently have shown that people who eat a diet high in
fruits, vegetables and grains have a reduced risk of many types of
cancer, including lung, alimentary tract, liver, pancreas, bladder,
kidney, breast, endometrium, cervix and prostate.

What is it about these foods that limits cancer?  In a quest
reminiscent of the search for vitamins begun in the last century,
scientists are trying to identify the beneficial compounds in the
fruits, vegetables and grains we eat that control tumor growth.

Plants contain many beneficial compounds including fiber and
micronutrients such as vitamins and their precursors.  According to
Elson, research initially focused on compounds such as vitamin A,
vitamin E and folic acid.  But clinical trials with them have been
inconclusive at best, he says.

Other scientists have been examining non-nutritive compounds in
plants.  Elson has been studying compounds he calls isoprenoids, a
group that includes more than 22,000 compounds.  All are derived
from a parent compound called mevalonic acid.  Limonene and lycopene
are examples of isoprenoids that inhibit cancer.

Many isoprenoids contribute to plants' distinctive flavors and
fragrances, Elson says.  In plants, isoprenoids help regulate
germination, growth, flowering, and dormancy while attracting
pollinators and protecting plants from insects and fungi.

Elson began working with isoprenoids because some can reduce
cholesterol levels in animals.  Initially he hoped that depriving
tumor cells of cholesterol would make them susceptible to cancer
treatments. But Elson's early experiments showed he could not lower
the cholesterol in tumor cells by feeding animals isoprenoids.
However, he noticed that the isoprenoids slowed tumor growth.

To screen isoprenoids for those with anticarcinogenic activity, Elson
tests them against a cell line developed from an extremely aggressive
form of mouse melanoma.  He has identified many isoprenoids that can
slow the growth of this cell line.  The tricky part has been finding
isoprenoids that suppress cancer growth at the low concentrations
that might occur in diets.

One such isoprenoid is gamma-tocotrienol, a compound found in cereal
grains; it has a chemical structure related to vitamin E.  In
research published in 1997, Elson's group showed that substituting
gamma-tocotrienol for vitamin E in a diet fed to mice slowed the
growth of tumors transplanted to those mice.  It was the first
research demonstrating that an isoprenoid slowed cancer growth and
prolonged the life of mice when fed at a level that an animal might
consume.

In the current paper, Elson and his graduate student, Huanbiao Mo,
found that gamma-tocotrienol slowed the growth of cell lines from
human leukemia and breast cancer.  They also tested beta-ionone --
an isoprenoid found widely in fruits and vegetables.  Beta-ionone is
related structurally to beta carotene, the precursor of vitamin A.
Elson and Mo showed that beta-ionone also suppressed the growth of
cell lines for human leukemia and breast cancer, as well as human
colon cancer.  The human cell lines were even more sensitive to the
action of the isoprenoids than the mouse melanoma cells, according
to Elson.

"We found that the human cancer cell lines were three times more
sensitive to the isoprenoids than a non-cancerous cell line," Elson
says. "This raises the issue of why cancer cells might be more
sensitive to these plant compounds than non-cancerous cells."

Mo and Elson found that the isoprenoids interfered with the
maturation of lamin B, a material cells need when they divide.  Many
of the tumor cells treated with the isoprenoids accumulated in a
pre-division phase while many others entered apoptosis, or
programmed cell death.  The researchers showed that the isoprenoids
suppressed the activity of 3 hydroxy-3-methyglutaryl coenzyme A (HMG
CoA) reductase, an enzyme critical for the maturation of lamin B as
well as the synthesis of cholesterol.

"We've known since the 1950s that tumor cells are more sensitive to
reductions of HMG CoA reductase than healthy cells," Elson says. 

"When isoprenoids inhibit the activity of this enzyme they disrupt
the processing of mevalonic acid via the mevalonate pathway.  We
think the tumor cells need chemical intermediates produced from the
breakdown of mevalonic acid for lamin B maturation and that
isoprenoids slow tumor growth by depriving tumor cells of those
intermediates." The nutritional scientist does not anticipate that
his research will lead to a single crucial isoprenoid or vegetable
that people can eat to protect themselves from cancer.  "These
compounds act as a group to inhibit cancer growth," he says, "with
some enhancing the effectiveness of others."

Nor does Elson believe in an exclusively vegetarian diet. "I don't
think that it's the presence of meat in diets that leads to health
problems, but the lack of enough fruits, grains and vegetables. The
people who eat a lot of animal products are often the same
individuals that don't eat enough fruits and vegetables," he says.

### 

fruits,veggies&tumors 4/99 
Writer:  George Gallepp, (608) 262-3636 ggallepp@facstaff.wisc.edu 

<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<
Michele Gale-Sinex, communications manager
Center for Integrated Ag Systems 
UW-Madison College of Ag and Life Sciences
Voice: (608) 262-8018   FAX: (608) 265-3020
http://www.wisc.edu/cias/
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
If you knew what life was worth, you
would look for yours on earth.  --Bob Marley

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