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Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer
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Chemopreventive and adjuvant therapeutic potential of pomegranate ( Punica granatum) for human breast cancer Nam Deuk Kim1, Rajendra Mehta2, Weiping Yu3, Ishak Neeman4, 5, Talia Livney5, Akiva Amichay5, Donald Poirier6, Paul Nicholls7, Andrew Kirby7, Wenguo Jiang8, Robert Mansel8, Cheppail Ramachandran9, Thangaiyan Rabi9, Boris Kaplan10, 11 and Ephraim Lansky5 | (1) | Department of Pharmacy, Pusan National University, Pusan, Korea |
| (2) | Department of Surgical Oncology, College of Medicine, University of Illinois, Chicago, Illinois, USA |
| (3) | School of Biological Sciences, University of Texas at Austin, Austin, Texas, USA |
| (4) | Department of Food Engineering and Biotechnology, Technion-Israel Institute of Technology, Haifa, Israel |
| (5) | Rimonest Ltd., Science Park Technion, Nesher, Israel |
| (6) | Laboratory of Molecular Endocrinology, Laval University Medical Research Center, Quebec, Canada |
| (7) | Welsh School of Pharmacy, Cardiff University, Redwood Building, Cardiff, UK |
| (8) | Metastasis Research Unit, Department of Surgery, University of Wales College of Medicine, Cardiff, UK |
| (9) | Research Institute, Miami Children's Hospital, Miami, Florida, USA |
| (10) | Department of Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel |
| (11) | Department of Obstetrics and Gynecology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel |
Abstract Fresh organically grown pomegranates ( Punica granatum L.) of the Wonderful cultivar were processed into three components: fermented juice, aqueous pericarp extract and cold-pressed or supercritical CO 2-extracted seed oil. Exposure to additional solvents yielded polyphenol-rich fractions (  polyphenols  ) from each of the three components. Their actions, and of the crude whole oil and crude fermented and unfermented juice concentrate, were assessed in vitro for possible chemopreventive or adjuvant therapeutic potential in human breast cancer. The ability to effect a blockade of endogenous active estrogen biosynthesis was shown by polyphenols from fermented juice, pericarp, and oil, which inhibited aromatase activity by 60–80%. Fermented juice and pericarp polyphenols, and whole seed oil, inhibited 17-  -hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at concentrations ranging from 100 to 1,000   g/ml according to seed oil  fermented juice polyphenols > pericarp polyphenols. In a yeast estrogen screen (YES) lyophilized fresh pomegranate juice effected a 55% inhibition of the estrogenic activity of 17- -estradiol; whereas the lyophilized juice by itself displayed only minimal estrogenic action. Inhibition of cell lines by fermented juice and pericarp polyphenols was according to estrogen-dependent (MCF-7) estrogen- independent (MB-MDA-231) > normal human breast epithelial cells (MCF-10A). In both MCF-7 and MB-MDA-231 cells, fermented pomegranate juice polyphenols consistently showed about twice the anti-proliferative effect as fresh pomegranate juice polyphenols. Pomegranate seed oil effected 90% inhibition of proliferation of MCF-7 at 100 g/ml medium, 75% inhibition of invasion of MCF-7 across a Matrigel membrane at 10 g/ml, and 54% apoptosis in MDA-MB-435 estrogen receptor negative metastatic human breast cancer cells at 50 g/ml. In a %% murine mammary gland organ culture, fermented juice polyphenols effected 47% inhibition of cancerous lesion formation induced by the carcinogen 7,12-dimethylbenz[ a]anthracene (DMBA). The findings suggest that clinical trials to further assess chemopreventive and adjuvant therapeutic applications of pomegranate in human breast cancer may be warranted. apoptosis - aromatase - breast cancer - chemoprevention - 17--hydroxysteroid dehydrogenase - estrogen - flavonoids - invasion - punicic acid
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