title: Pomegranate fruit extract impairs invasion and motility in human breast cancer.
abstract: OBJECTIVE
  Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity.
  
  
  METHODS
  The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined.
  
  
  RESULTS
  Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression.
  
  
  CONCLUSIONS
  Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. gkhan@umich.edu
authors.forename: Gazala N
authors.initials: GN
authors.lastname: Khan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gorin
authors.forename: Devin
authors.initials: D
authors.lastname: Rosenthal
authors.forename: Quintin
authors.initials: Q
authors.lastname: Pan
authors.forename: Li Wei
authors.initials: LW
authors.lastname: Bao
authors.forename: Zhi Fen
authors.initials: ZF
authors.lastname: Wu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Newman
authors.forename: Alison D
authors.initials: AD
authors.lastname: Pawlus
authors.forename: Peiying
authors.initials: P
authors.lastname: Yang
authors.forename: Ephraim P
authors.initials: EP
authors.lastname: Lansky
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005638:Fruit / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D010936:Plant Extracts; D051996:Transcription Factor RelA; C066737:RHOA protein, human; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein; D015232:Dinoprostone