Grape seed proanthocyanidins inhibit migration potential of pancreatic cancer cells by promoting mesenchymal-to-epithelial transition and targeting NF-κB.
Here we explore the effect of grape seed proanthocyanidins (GSPs) on pancreatic cancer cell migration and the molecular mechanisms underlying these effects. Treatment of human pancreatic cancer cell lines Miapaca-2, PANC-1 and AsPC-1 with GSPs resulted in inhibition of cell migration (19-82%, P<0.01-0.001), which was associated with decreased phosphorylation of ERK1/2 and inactivation of NF-κB. Treatment of cells with UO126, an inhibitor of MEK, and caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited the migration of cells (40-80%, P<0.01-0.001). Inhibition of cell migration by GSPs was associated with reversal of the epithelial-to-mesenchymal transition. This was associated with upregulation of E-cadherin and desmoglein-2 and down-regulation of fibronectin, N-cadherin and vimentin.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Ram
R
Prasad
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, USA; Nutrition Obesity Research Center, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA. Electronic address: skatiyar@uab.edu.
Santosh K
SK
Katiyar
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D002070:Butadienes; D004791:Enzyme Inhibitors; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D016328:NF-kappa B; D009570:Nitriles; D044945:Proanthocyanidins; C113580:U 0126; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3