POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
THURSDAY, 5:30-6:15 PM
Murphy LL, King ML.
Using protein microarray analysis to determine the many
anti-cancer mechanisms of ginseng action in human breast cancer MCF-7
cells.
Southern Illinois University lmurphy@siumed.edu
Ginseng is an herbal that is widely used for
its purported medicinal properties. The anti-cancer actions of ginseng
have been well-described, however there is very little information regarding
its mechanism(s) of action. Therefore, in this study, MCF-7 cancer cells
were treated with water-extracted North American ginseng root and cells
were analyzed for changes in protein expression using protein microarray
analysis.
The Panorama
Ab Cell Signaling Microarray (Sigma-Aldrich Chemical Company, St. Louis,
MO) containing 224 different antibodies representing apoptosis, cell
cycle, signal transduction, and nuclear proteins, was utilized to detect
changes in protein expression following ginseng treatment versus untreated
control cells. The concentration of ginseng used in these studies (0.5
mg/ml) was shown to preferentially inhibit proliferation of MCF-7 versus
non-malignant human mammary epithelial cells. Cell protein was harvested
24 hr after ginseng treatment.
Ginseng treatment induced a significant increase
(>2.5-fold; p<0.05) in the expression of p21 and decreases in expression
of cdk6 and pRb (p<0.05) indicating that the reported cytostatic effect
of ginseng on cell proliferation is mediated, at least in part, via
activation of p21 and induction of cell cycle stasis at the G1/S transition.
This was confirmed by flow cytometry that showed a ginseng-induced 38%
increase in number of cells in the G0/ G1-phase and a similar decrease
in cells in the S-phase compared to untreated cells. Western analysis
confirmed that ginseng produced an 8-fold increase in p21 and a 50%
decrease in pRb protein expression, both in vitro and in vivo
in MCF-7 tumors from ginseng-treated nude mice. In addition, ginseng
treatment produced a significant elevation in Raf-kinase inhibitory
protein (RKIP; p<0.05) and decreases in the expression of the MAP kinase
signaling proteins phospho-Mek and ŠErk, which may also contribute to
the inhibition of cancer cell proliferation by ginseng. An increase
in nitric oxide synthase and decrease in expression of five cytostructural
and cell signaling proteins were also observed. Ginseng contains over
20 different ginsenosides, the biologically active components in ginseng.
The results of this study indicate that ginseng,
perhaps via its many ginsenosides, exerts numerous cellular actions
that, in toto, cause inhibition of cancer cell proliferation.
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