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).
Journal
Anticancer Research