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Pancreatic Cancer


J Gastrointest Surg.2010 May;14(5):873-9. doi: 10.1007/s11605-010-1164-4. Epub 2010 Feb 6.

Pterostilbene inhibits pancreatic cancer in vitro.

Mannal PW1,Alosi JA, Schneider JG, McDonald DE, McFadden DW.

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INTRODUCTION: Stilbenes are phenolic compounds present in grapes and blueberries. Resveratrol, a naturally occurring compound present in grapes, has been shown to have potent antioxidant properties as well as an ability to induce apoptosis. Resveratrol has also been reported to have significant inhibitory effects against a variety of primary tumors including breast, colon, and prostate. Pterostilbene, a naturally occurring analogue of resveratrol found in blueberries, also has antioxidant and antiproliferative properties. It is also substantially more bioavailable orally than resveratrol. These effects have not been studied in pancreatic cancer. We hypothesized that pterostilbene would inhibit pancreatic cancer cell growth in vitro.

MATERIALS AND METHODS: Two pancreatic cancer cell lines (MIA PaCa and PANC-1) were cultured using standard techniques. Cells were treated with graduated doses of pterostilbene ranging from 10 to 100 microM. Cell viability was measured by MTT at 24, 48, and 72 h.

RESULTS: Pterostilbene decreases cell viability in both cancer cell lines in a concentration- and time-dependent manner. Higher doses (75-100 microM) caused a significant reduction in cell viability at 24 and 48 h. However, by 72 h, all tested concentrations of pterostilbene(10 to 100 microM) resulted in significantly reduced cell viability in both pancreatic cancer cell lines in a dose-dependent fashion. Pterostilbenecaused a dose-dependent 10-63% inhibition in MIA PaCa-2 cells and 10-75% inhibition in PANC-1 cells.

DISCUSSION: Treatment of pancreatic cancer cells in vitro with Pterostilbeneleads to inhibition of cell proliferation and/or cell death, cell cycle arrest, mitochondrial membrane depolarization, and activation of effector caspases. This naturally occurring agent may have a role in treating pancreatic cancer.

CONCLUSIONS: Pterostilbene inhibits the growth of pancreatic cancer in vitro. Further, in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of pancreatic cancer.

PMID: 20140535

J Gastrointest Surg.2012 Jun;16(6):1136-43. doi: 10.1007/s11605-012-1869-7. Epub 2012 Mar 27.

Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.

McCormack DE1,Mannal P, McDonald D, Tighe S, Hanson J, McFadden D.

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BACKGROUND: To investigate the inhibitory role of pterostilbene in pancreatic cancer, we conducted a genomic analysis of pterostilbene-treated pancreatic cancer cells. We also investigated the effect of pterostilbene upon the carcinogenic markers, manganese superoxide dismutase, cytochrome C, Smac/DIABLO, and STAT3 phosphorylation in vitro. The antiproliferative effects of pterostilbene were further evaluated in an in vivo model.

METHODS: Pancreatic cancer cells were treated with pterostilbene and evaluated with DNA microarray analysis. Pterostilbene-treated cells were analyzed for cytochrome C, Smac/DIABLO, manganese superoxide dismutase (MnSOD)/antioxidant activity, and STAT3 phosphorylation using ELISA. Data were statistically analyzed using ANOVA. Pterostilbene was then administered to nude mice for 8 weeks, and tumor growth rates were recorded and statistically analyzed.

RESULTS: Microarray analysis of pterostilbene-treated cells revealed upregulation of pro-apoptosis genes. In vitro, pterostilbene treatment altered levels of phosphorylated STAT3, MnSOD/antioxidant activity, cytochrome C, and Smac/DIABLO. In nude mice, oral pterostilbene inhibited tumor growth rates.

CONCLUSION: Pterostilbene alters gene expression in pancreatic cancer and increases the antiproliferative markers cytochrome C, Smac/DIABLO, and MnSOD/antioxidant activity. It was also shown to inhibit phosphorylated STAT3, a marker of accelerated tumorigenesis, and decrease pancreatic tumor growth in vivo. Further studies are warranted to elucidate the effects of pterostilbene in humans.

PMID: 22450950

J Surg Res.2012 Oct;177(2):255-62. doi: 10.1016/j.jss.2012.04.023. Epub 2012 May 3.

Inhibitory effects of (-)-epigallocatechin-3-gallate and pterostilbene on pancreatic cancer growth in vitro.

Kostin SF1,McDonald DE, McFadden DW.

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BACKGROUND: It has been previously shown that the naturally occurring antioxidant (-)-epigallocatechin-3-gallate (EGCG), found in green tea, and pterostilbene, a stilbenoid derived from blueberries, inhibit pancreatic cancer in vitro when used individually. We hypothesized that the combination of EGCG and pterostilbene would reveal additive effects in vitro.

METHODS: Using the pancreatic cancer cell lines MIA PaCa-2 and PANC-1, efficacy and synergism were evaluated for cell proliferation and viability (3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium bromide assays, cell cycle analysis) and mitochondrial apoptosis (mitochondrial depolarization, cytochrome C release, caspase-3/7 activity, cell death detection using enzyme-linked immunosorbent assay).

RESULTS: Cell proliferation assays revealed significant additive antiproliferative effects with pterostilbene and EGCG in both cell lines at the later, 72-h, point (P < 0.05). MIA underwent S-phase arrest with the combination (10-12% increase); however, cell cycle arrest was not observed in PANC. The combination induced mitochondrial depolarization and upregulated cytochrome C (P < 0.05) in MIA, but these effects were not observed in PANC. EGCG increased caspase-3/7 in MIA; however, the combination did not significantly increase the activity in either cell line (P < 0.05). Apoptosis was only observed in PANC (P < 0.05). The reduction in proliferation in MIA in the 3-(4,5-dimethyltiazol-2-y1)-2,5-diphenltetrazolium bromide assays with the combination indicated that cell death occurs, possibly through another mechanism.

CONCLUSIONS: Our results are encouraging regarding the future use of EGCG and pterostilbene to improve traditional pancreatic cancer therapies. In conclusion, EGCG and pterostilbene have additive, antiproliferative effects in vitro and alter the apoptotic mechanisms in both cell lines by modulation at different points in the mechanism.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22583593