Ginkgo biloba extract: More than just for memory?
Washington, DC -- 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 Valium®, 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.
####
The study was funded by the National Center for Complementary
and Alternative Medicine (NCCAM), National Institutes of
Health and the Institut Henri Beaufour-IPSEN, France.
Co-authors from Georgetown University Medical Center are
first author Ewald Pretner, MD, Hakima Amri, PhD,
Wenping Li, MD, PhD, Rachel Brown, PhD, Chin-Shoou Lin,
MS, and Erini Makariou, MD. Also contributing to the
research were Francis Defeudis, PhD, from the Institute
for Bioscience, in Westborough, MA., and Katy Drieu,
DPharm, from the Institut Henri Beaufour-IPSEN, in
Paris.
About Georgetown University Medical Center
Georgetown University Medical Center is an
internationally recognized academic medical center with
a three-part mission of research, teaching and patient
care (through our partnership with MedStar Health). Our
mission is carried out with a strong emphasis on public
service and a dedication to the Catholic, Jesuit
principle of cura personalis -- or "care of the whole
person." The Medical Center includes the School of
Medicine and the School of Nursing and Health Studies,
both nationally ranked, the world-renowned Lombardi
Comprehensive Cancer Center and the Biomedical Graduate
Research Organization (BGRO).