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Cancer-related overexpression of the
peripheral-type benzodiazepine receptor and cytostatic anticancer
effects of Ginkgo biloba extract (EGb 761)
Pretner E, Amri H, Li W, Brown R, Lin
CS, Makariou E, Defeudis FV, Drieu K, Papadopoulos
V
Department of Biochemistry and Molecular Biology, Georgetown
University School of Medicine, Washington DC, 20007, USA.
The peripheral-type benzodiazepine receptor (PBR) is an 18-kDa high
affinity drug- and cholesterol-binding protein that is involved in
various cell functions, including cell proliferation and
apoptosis.
PBR was shown to be overexpressed in
certain types of malignant human tumors and cancer cell lines,
correlating with enhanced tumorigenicity and cell proliferation
rates.
The present study was conducted in order
to further define the role of PBR in cancer and to extend our recent
findings regarding the possible anticancer effects of the standardized
Ginkgo biloba extract EGb 761.
Treatment with EGb 761 decreased PBR mRNA
levels and inhibited the proliferation of breast, glioma and
hepatocarcinoma cell lines, further corroborating our previous
contention that its mechanism of action is through the modification of
PBR expression.
In vivo treatment with Ginkgo biloba
extract led to dose-dependent decreases in xenograft growth of both
MDA-MB-231 breast cancer and U-87 glioma cell lines in nude mice,
although the effects were not maintained after 50 days of treatment in
the latter.
The results obtained in MDA-MB-231
xenografts indicated pronounced inhibition of tumor growth, verified
by MRI imaging.
These results were obtained using a
modified experimental protocol where the animals were treated with the
extract before cell inoculation.
Although an exact role for PBR in relation
to the initiation and progression of various types of cancer remains
to be defined, our results indicate that PBR overexpression in certain
cancer cells is related to an aggressive phenotype.
Since EGb 761 treatment opposes this
aggressive phenotype by decreasing PBR overexpression, it could be
useful in preventing or treating cancer invasiveness and metastasis.
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