|
Event: |
2004
Gastrointestinal Cancers Symposium |
| Abstract: |
Background:
PC-Hope is a novel Chinese herbal supplement marketed for the treatment
of prostate cancer. It contains all herbal extracts that are also
present in the better known supplement PC-SPES, in addition to sterolin
and quercetin. We have previously shown that PC-SPES displays strong
antiproliferative and apoptotic effects in human pancreatic cancer (PaCa)
cells in vitro. Purpose of this study was to assess the impact of
PC-Hope on PaCa cells both in vitro and in vivo. Methods: Eight
human PaCa cell lines were exposed to ethanol extracts of PC-Hope in
vitro. Cell proliferation (via sulfarhodamine B staining), effects on
cell cycle (propidium iodide uptake), and mode of cell death (DAPI
staining) were analyzed. In vivo effects were studied in an
intraperitoneal Panc-1/SCID mouse model. PC-Hope (extract from up to
250mg /kg) was injected daily i.p. from day 7 to day 21. Results:
PC-Hope displayed dose-dependent inhibition of cell proliferation in all
8 PaCa lines. Median inhibitory concentrations (IC50) for 48-hour assays
ranged from 0.4 to 4 uL/mL. Three-hour exposure to PC-Hope (dose range:
2 to 10 uL/mL) led to a significant absolute increase in the G2/M cell
cycle fraction (range: 6.7% to 25%). Cyclin B1 levels were downregulated
in all lines after 24 hr. exposure to PC-Hope. The mode of PC-Hope
induced toxicity was consistent with apoptotic cell death. After 24
hours of PC-Hope exposure at 0.4 uL/mL, DAPI positive apoptotic nuclear
formations were seen in 20% to 46% of cells. At the highest dose tested
in vivo, PC-Hope extract induced toxicity, with one animal dying on
day14. For the remaining mice, there was a significant survival
advantage (median survival 34 versus 76 days, p=0.008). However, all
treated animals ultimately developed tumors in an intraperitoneal
distribution similar to controls. Conclusions: PC-Hope mediates
potent antiproliferative effects against an array of PaCa cells in
vitro. G2/M cell cycle accumulation through cyclin B1 downregulation,
and induction of apoptosis are characteristics for its mechanism. In
vivo activity has led to a significant survival advantage, but no
curative result to date. PC-Hope qualifies for phase I clinical testing.
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