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Breast Cancer Research and Treatment

, Volume 71, Issue 3, pp 203–217 | Cite as

Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer

  • Nam Deuk Kim
  • Rajendra Mehta
  • Weiping Yu
  • Ishak Neeman
  • Talia Livney
  • Akiva Amichay
  • Donald Poirier
  • Paul Nicholls
  • Andrew Kirby
  • Wenguo Jiang
  • Robert Mansel
  • Cheppail Ramachandran
  • Thangaiyan Rabi
  • Boris Kaplan
  • Ephraim Lansky
Article

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 CO2-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-β-hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at concentrations ranging from 100 to 1,000 μg/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-β-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 μg/ml medium, 75% inhibition of invasion of MCF-7 across a Matrigel membrane at 10 μg/ml, and 54% apoptosis in MDA-MB-435 estrogen receptor negative metastatic human breast cancer cells at 50 μg/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-β-hydroxysteroid dehydrogenase estrogen flavonoids invasion punicic acid 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Nam Deuk Kim
    • 1
  • Rajendra Mehta
    • 2
  • Weiping Yu
    • 3
  • Ishak Neeman
    • 4
    • 5
  • Talia Livney
    • 5
  • Akiva Amichay
    • 5
  • Donald Poirier
    • 6
  • Paul Nicholls
    • 7
  • Andrew Kirby
    • 7
  • Wenguo Jiang
    • 8
  • Robert Mansel
    • 8
  • Cheppail Ramachandran
    • 9
  • Thangaiyan Rabi
    • 9
  • Boris Kaplan
    • 10
    • 11
  • Ephraim Lansky
    • 5
  1. 1.Department of PharmacyPusan National UniversityPusanKorea
  2. 2.Department of Surgical Oncology, College of MedicineUniversity of IllinoisChicagoUSA
  3. 3.School of Biological SciencesUniversity of Texas at AustinAustinUSA
  4. 4.Department of Food Engineering and BiotechnologyTechnion-Israel Institute of TechnologyHaifaIsrael
  5. 5.Rimonest Ltd., Science Park TechnionNesherIsrael
  6. 6.Laboratory of Molecular EndocrinologyLaval University Medical Research CenterCanada
  7. 7.Welsh School of PharmacyCardiff UniversityCardiffUK
  8. 8.Metastasis Research Unit, Department of SurgeryUniversity of Wales College of MedicineCardiffUK
  9. 9.Research InstituteMiami Children's HospitalMiamiUSA
  10. 10.Department of Medicine, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  11. 11.Department of Obstetrics and GynecologyRabin Medical CenterPetach TikvaIsrael

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