POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 5:45-6:30 PM
Levine RA, Jiang H, Kuo K, Kuo J, Jackson-Hunter T,
Gautam SC, Corcoran GB, Seidman MD, Rodriguez AI.
Resveratrol-induced apoptotic death in human U251 glioma
cells.
Henry Ford Health System bob-levine@earthlink.net
Resveratrol (trans-3,4',5-trihydroxystilbene) is a
naturally occurring polyphenolic compound highly enriched in grapes,
peanuts, red wine and a variety of food sources. Resveratrol has anti-inflammatory
and antioxidant properties, and also has potent anticancer properties.
Human glioma U251 cells were used to understand the molecular mechanisms
by which resveratrol acts as an anti-cancer agent, since glioma is a
particularly difficult cancer to treat and eradicate. The hypothesis
tested is that resveratrol kills human U251 glioma by stimulating apoptotic
death. Our data demonstrate that resveratrol induces dose- and time-dependent
death of U251 cells, as measured by LDH release and internucleosomal
DNA fragmentation assays. Resveratrol induces activation of caspase-3
and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose)
polymerase (PARP). Resveratrol-induced DNA fragmentation can be completely
blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective
caspase-3 inhibitor (ZDEVD-FMK), but not by a selective caspase-1 inhibitor.
Resveratrol induces cytochrome C release from mitochondria to the cytoplasm
and activation of caspase-9. Resveratrol also increases _expression
of pro-apoptotic Bax and its translocation to the mitochondria. Resveratrol
inhibits U251 proliferation, as measured by MTS assay, and induces G0/G1
growth arrest, as determined by flow cytometry. The CDK inhibitor, olomoucine,
prevents cell cycle progression and resveratrol-induced apoptosis. These
results suggest that multiple signaling pathways may underlie the apoptotic
death of U251 glioma induced by resveratrol, which warrants further
exploration as an anti-cancer agent in human glioma.
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