Genomic Analysis of Pterostilbene Predicts Its Antiproliferative Effects Against Pancreatic Cancer In Vitro and In Vivo

被引:42
|
作者
McCormack, Denise Elizabeth [1 ]
Mannal, Patrick [2 ]
McDonald, Debbie [3 ]
Tighe, Scott [4 ]
Hanson, Joshua [5 ]
McFadden, David [6 ]
机构
[1] Danbury Hosp, Dept Surg, Danbury, CT 06810 USA
[2] Univ Vermont, Dept Surg, Fletcher Allen Hlth Care, Burlington, VT 05401 USA
[3] Univ Vermont, Dept Surg, Fletcher Allen Hlth Care, Burlington, VT 05405 USA
[4] Univ Vermont, Adv Genome Technol Lab, Burlington, VT 05405 USA
[5] Univ Vermont, Dept Pathol, Fletcher Allen Hlth Care, Burlington, VT 05401 USA
[6] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA
关键词
Pancreatic cancer; Pterostilbene; Apoptosis; MANGANESE SUPEROXIDE-DISMUTASE; MALIGNANT PHENOTYPE; CELLS; INHIBITION; GROWTH; OVEREXPRESSION; RESVERATROL; TRANSDUCER; ACTIVATOR;
D O I
10.1007/s11605-012-1869-7
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. 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. 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. 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.
引用
收藏
页码:1136 / 1143
页数:8
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