POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 5:45-6:30 PM
Amri H, Pretner E, Li W, Brown R, Lin CS, Makariou E,
DeFeudis FV, Drieu K, Papadopoulos, V.
Effects of Ginkgo biloba extract EGb 761 on tumor growth
and metastasis: an adjuvant therapeutic alternative.
Department of Physiology and Biophysics, Georgetown
University School of Medicine amrih@georgetown.edu
PURPOSE: This study investigates the effect
of EGb 761 extract (used in its injectable form, i.e. IPS 200, which
is devoid of cytotoxic proanthocyanidins) on cell growth and proliferation
in human cell lines of different ontogeny over-expressing PBR, and on
tumor growth and metastasis in nude mice. Ginkgo biloba's medicinal
value has been extensively described in the Chinese pharmacopoeia, especially
in the context of cardiovascular and respiratory disease states as well
as elevated serum cholesterol levels. The peripheral-type benzodiazepine
receptor (PBR) is defined as a cholesterol transport channel, which
is over-expressed in a number of cancer cell lines and certain types
of malignant tumors. Our group has previously demonstrated that standardized
Ginkgo biloba extract EGb 761 regulates PBR at the cellular, molecular,
and gene _expression levels.
METHODS: Immunocytochemistry, radioligand-binding
methods, cell proliferation and viability assays, quantitative PCR,
as well as apoptosis assays were used for the in vitro studies. Evaluation
of tumor growth and metastasis, including MRI imaging, were used as
in vivo outcome measures. One-way analysis of variance and unpaired
t-test were performed using the InStat program.
RESULTS: Treatment with EGb 761 inhibited the
proliferation of human breast cancer MDA-MB-231, glioblastoma U-87,
and hepatocarcinoma HepG2 and Hep3B cell lines in a dose dependent manner.
Total PBR mRNA levels in MDA-MB-231, U-87, and HT-29 (colon cancer)
cell lines were decreased upon treatment, indicating that EGb 761 acts
via the modification of PBR _expression. In vivo treatment with EGb
761 led to dose-dependent decreases in xenograft growth of both MDA-MB-231
breast cancer and U-87 glioblastoma cell lines in nude mice, although
the effects in the latter were not maintained beyond 50 days of treatment.
Results obtained with pretreated MDA-MB-231 xenografts indicated pronounced
inhibition of tumor growth as verified by MRI imaging. Although the
exact role of PBR in relation to the initiation and progression of various
types of cancers remains to be defined, our results indicate that PBR
over-_expression in certain cancer cells is related to an aggressive
phenotype. Treatment with EGb 761 appears to oppose this aggressive
phenotype by decreasing PBR over-_expression.
CONCLUSIONS: Ginkgo biloba standardized extract
EGb 761 plays an anti-cancer role by regulating PBR _expression in both
in vitro and in vivo models. We therefore conclude that EGb 761 may
offer a useful adjuvant therapeutic approach in the prevention and treatment
of certain cancers via its effects on invasiveness and metastatic spread.
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