title: Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Danbury Hospital, Danbury, CT 06810, USA. Denise.McCormack@wcthealthnetwork.org
authors.forename: Denise Elizabeth
authors.initials: DE
authors.lastname: McCormack
authors.forename: Patrick
authors.initials: P
authors.lastname: Mannal
authors.forename: Debbie
authors.initials: D
authors.lastname: McDonald
authors.forename: Scott
authors.initials: S
authors.lastname: Tighe
authors.forename: Joshua
authors.initials: J
authors.lastname: Hanson
authors.forename: David
authors.initials: D
authors.lastname: McFadden
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D016678:Genome / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D035721:Pterocarpus; D013267:Stilbenes / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004273:DNA, Neoplasm; D013267:Stilbenes; C107773:pterostilbene