Genomic Analysis of Pterostilbene Predicts Its Antiproliferative Effects Against Pancreatic Cancer In Vitro and In Vivo
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.
KeywordsPancreatic cancer Pterostilbene Apoptosis
Microarray analysis was conducted by the Vermont Genetics Network microarray facility through grant number 2P20RR016462 from the INBRE Program of the National Center for Research Resources (NCRR). Bioinformatic support and data analysis was conducted by Dr. Jeff Bond at the University of Vermont Bioinformatics shared resource facility.
- 4.Westphal S and Kalthoff H. Apoptosis: targets in pancreatic cancer. Mol Cancer 2003. 2:6.Google Scholar
- 13.Wang M, Chen P, Dafforn, A et al. Ribo-SPIA™: A Novel Isothermal, Linear Amplification Method for Transcriptome Analysis of Very Small Samples. Macroresults for Microarrays/Genomic and Proteomic Sample Preparation, World Trade Center, Boston, Massachusetts, 2003.Google Scholar
- 14.Chen P, Deng G, Iglehart D, et al. A Novel Global mRNA Amplification Method For Gene Expression Analysis in Very Small Total RNA Samples. Molecular profiling of normal development and pathology in tissue integrating laser microdissection and microanalysis, 2002.Google Scholar