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Background: Resveratrol, a naturally occurring phenol is a potent antioxidant as well as having pro-apoptotic properties. Pterostilbene is an analogue of resveratrol with greater oral bioavailability. Our previous studies have shown Pterostilbene to be an effective growth inhibitor against multiple cancer cell lines. To further evaluate Pterostilbene’s potential role as an agent against pancreatic cancer, we hypothesized that there would be additive effects when Gemcitabine and Pterostilbene were combined.Methods: Two pancreatic cancer cell lines (MIA-PACA and PANC-1) were cultured using standard techniques. Cells were pretreated with 1µM Gemcitabine for 18 hours followed by graduated doses of Pterostilbene (10 - 30µM). In addition, cells were pretreated with Pterostilbene (10 - 30µM) for 18 hours followed by 1µM Gemcitabine. Lastly, the same pancreatic cell lines were treated simultaneously with Pterostilbene and Gemcitabine (doses identical to those above) after which cell viability was assessed in all three groups by MTT assay at 24, 48 and 72 hours. Results: Gemcitabine and Pterostilbene show an additive effect on pancreatic cancer cell viability in a time and dose dependent manner. The best results were seen when pancreatic cancer cells were pre-treated with Pterostilbene followed by Gemcitabine treatment. With Pterostilbene pre-treatment, the greatest effects were seen at 48 and 72 hours for MIA cells, where cell viability was reduced to 23% and 21% of control, respectively (P<0.001). The Pterostilbene pre-treated PANC cells reached maximum inhibition of cell viability at 72 hours with a reduction to 34% of control (P<0.001). Simultaneous use of Gemcitabine and Pterostilbene in PANC cells reduced cell viability at 72 hours to 56% and 50% of control with Pterostilbene concentrations of 10µM and 20µM, respectively (P<0.01). MIA cells treated simultaneously with Gemcitabine and Pterostilbene also showed reduction to 62% and 58% of control at 48hours and 37% and 35% of control at 72 hours with Pterostilbene concentrations of 10µM and 20µM (P<0.01). Conclusion: Pterostilbene, a well tolerated natural compound found in blueberries, may have clinical utility in the treatment of pancreatic cancer. Combination treatment of Pterostilbene with Gemcitabine leads to an additive cytotoxic effect on pancreatic cancer cells in vitro. This synergism occurs best in Pterostilbene pre-treated calls and simultaneously treated cells. Further delineation of the mechanisms of action of Pterostilbene is on-going to assess its potential usefulness in treatment of this devastating disease.