Additive Inhibitory Effects of Inositol Hexaphosphate and Pterostilbene On Pancreatic Cancer Cell Growth in Vitro
John Schneider, Julie a. Alosi, David W. Mcfadden*
Surgery, University of Vermont, Burlington, VT
Background: Diets rich in fruits, vegetables, and fiber have been linked to reduced rates of several cancers. Resveratrol, a phytonutrient found in grapes, is a potent antioxidant that inhibits the growth of several types of cancer. We have shown that pterostilbene, a natural analog of resveratrol found in blueberries, inhibits the growth of cultured pancreatic cancer cell lines in a concentration and time-dependent manner. Pterostilbene appears to act via pro-apoptotic mechanisms. Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate found in foods with high fiber content. We have also shown that IP6 significantly inhibits cell growth of pancreatic cancer cells in vitro, via non-apoptotic pathways. We hypothesized that the combination of pterostilbene and IP6 would synergistically inhibit pancreatic cancer cell growth in vitro.Methods: Two human pancreatic cancer cell lines, Mia PaCa-2 and PANC-1 were treated with increasing doses of pterostilbene (25 - 75 μM) or IP6 (250 - 1000 micromolar) and combinations thereof. Cell viability was measured at 24, 48, and 72 hours using a MTT assay. Student’s t-test and two-way ANOVA were used for statistical analysis.Results: Pterostilbene and IP6 inhibited proliferation in both Mia PaCA-2 and PANC-1 cell lines in a concentration and time dependent manner (p< 0.001 at 72 hours for all) when administered alone. After 72 hours of combined treatment, significant additive effects of IP6 at 750 and 1000micromolar were seen with all pterostilbene doses in both cell lines (p<0.001).Conclusions: The naturally occurring nutrients pterostilbene and IP-6 in combination exhibit synergistic anti-cancer effects in vitro against pancreatic cancer. Further mechanistic studies and in vivo experiments are warranted to determine the potential role for pterostilbene and IP6 in pancreatic cancer treatment.
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