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Pomegranate Fruit Extract Impairs Invasion and Motility in Human Breast Cancer

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA, gkhan{at}umich.edu

Michael A. Gorin

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Devin Rosenthal

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Quintin Pan

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Li Wei Bao

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Zhi Fen Wu

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Robert A. Newman

Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston,TX, USA, Punisyn Pharmaceuticals, Haifa, Israel

Alison D. Pawlus

Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston,TX, USA

Peiying Yang

Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston,TX, USA

Ephraim P. Lansky

Punisyn Pharmaceuticals, Haifa, Israel

Sofia D. Merajver

Department of Internal Medicine, University of Michigan,Ann Arbor, MI, USA

Purpose. 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. Experimental design. 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. Conclusion. 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.

Key Words: breast cancer • cancer prevention • in vitro studies • Punica granatum

Integrative Cancer Therapies, Vol. 8, No. 3, 242-253 (2009)
DOI: 10.1177/1534735409341405


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