Pomegranate fruit extract impairs invasion and motility in human breast cancer.
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.
Khan
Gazala N
GN
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. gkhan@umich.edu
Gorin
Michael A
MA
Rosenthal
Devin
D
Pan
Quintin
Q
Bao
Li Wei
LW
Wu
Zhi Fen
ZF
Newman
Robert A
RA
Pawlus
Alison D
AD
Yang
Peiying
P
Lansky
Ephraim P
EP
Merajver
Sofia D
SD
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
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