Researchers at Georgetown University Medical
Center say they now have a clearer picture of how an extract
from the leaves of the Ginkgo biloba tree reduces the
risk of aggressive cancer in animal experiments.
In the January-February issue of the journal Anticancer
Research, the investigators reported that treating mice
with an extract of leaves of Ginkgo biloba both before
and after implanting human breast or brain (glioma) tumors
decreased expression of a cell receptor associated with
invasive cancer. This decreased expression slowed the
growth of the breast tumors by 80 percent as long as the
extract was used, compared to untreated mice, and also
reduced the size of the brain tumors, but temporarily,
and to a lesser extent.
Ginkgo biloba extract is a popular supplement that comes
from the leaves of the Gingko tree, which is indigenous
to Japan, Korea and China but can be found all over the
world. Many believe it enhances memory, and is being currently
being tested as a treatment for Alzheimer's disease.
"It is very encouraging that Ginkgo biloba appeared to
reduce the aggressiveness of these cancers, because it
suggests that the leaves could be useful in some early
stage diseases to prevent them from becoming invasive,
or spreading," said the study's senior author, Vassilios
Papadopoulos, DPharm, PhD, Director, Biomedical Graduate
Research Organization and Associate Vice President of
Georgetown University Medical Center.
"But I must stress that this is a study in mice, and
so we cannot say what anticancer effects, if any, Gingko
biloba might offer humans," he said.
Papadopoulos and his research team became interested
in Gingko biloba because their research suggested that
it might interact with the peripheral-type benzodiazepine
receptor (PBR), a molecule they have been studying for
the last 20 years. For example, they have determined that
this protein (discovered by accident when researchers
looked at how the anti-anxiety drug diazepam, better known
as ValiumŪ, worked) is involved in bringing cholesterol
into a cell's mitochondria.
In some cells the mitochondria uses cholesterol to produce
steroids, which are regulatory hormones that, among other
functions, help a cell grow, Papadopoulos said. "In fact,
we have found that most life forms, including plants,
insects, and animals, have receptors like these that help
regulate growth."
So they looked at whether cancer cells -- with their
need to proliferate -- produce more of these cholesterol-bearing
receptors, and found that some highly invasive cancers
do, indeed, over-express PBR. "Accelerated growth requires
production of new cell membranes, and one of the main
components of membranes is cholesterol," Papadopoulos
said.
The researchers also knew that steroids help regulate
brain function, and they found over-expression of PBR
is also associated with a variety of neurological disorders.
Because the leaf of Ginkgo biloba is an ancient Chinese
treatment for dementia that is still widely used -- and
which is now being tested in the U.S. to treat Alzheimer's
disease patients -- Papadopoulos decided to look at the
effect of Ginkgo biloba on PBR production.
He selected breast cancer cells that over-expressed PBR,
implanted them in mice, and treated the mice with a standardized
extract of Ginkgo biloba leaves. After 30 days, tumor
size was reduced by 35 percent, compared to untreated
mice. That research was published in 2000.
One aim of this new study, then, was to find whether
other cancer cell lines also over-express PBR. They found
that, in addition to one form of aggressive breast cancer
(invasive estrogen-receptor negative), certain brain,
colon, and prostate cancers also show higher than normal
levels of PBR.
The other part of the research was to see if Ginkgo biloba
would show any anticancer effects on these cancer cell
lines, and concluded that the extract did nothing to cancers
that were not invasive, but significantly slowed the growth
of aggressive cancer cells.
Papadopoulos and his team then studied whether a non-commercial
injectable form of a standardized extract of Ginkgo biloba
leaves might have any preventive effects, and selected
the aggressive breast cancer and brain glioma to study
in mice. The researchers pretreated the animals with this
pharmaceutical preparation of Ginkgo biloba, then implanted
the tumors. The Ginkgo biloba extract inhibited growth
of the breast tumors by more than 80 percent, but glioma
tumors did not respond as strongly, and the benefit was
maintained for only 50 days despite continuous treatment.
Tumors implanted in mice that did not over-express PBR
did not respond to the extract.
Papadopoulos now plans to examine the notion that a cancer
diagnosis might increase production of stress steroids
such as corticosteroids through PBR over-expression, and
it is this stress that, in effect, pushes a tumor to become
invasive. "Ginkgo biloba could possibly reduce this stress
by tamping down PBR," he said.
