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Chinese herbal supplement PC-Hope extending survival in pancreatic cancer model.
Abstract No: 147
Event: 2004 Gastrointestinal Cancers Symposium
Author(s): R. E. Schwarz, S. Konduri
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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